Association of PvuII and XbaI polymorphisms in estrogen receptor alpha gene with the risk of hepatitis B virus infection in the Guangxi Zhuang population

Background and objectiveAvailable evidence has suggested that estrogen receptor alpha (ESR1) is implicated in the pathogenic process of hepatitis B infection. Therefore, we evaluated the association of PvuII (rs2234693) and XbaI (rs9340799) in ESR1 and HBV infection in Guangxi Zhuang populations.MethodsA total of 389 subjects were divided into four groups: 112 patients with chronic hepatitis B (CHB), 65 patients with hepatitis B virus (HBV)-related liver cirrhosis (LC), 107 patients with HBV-related hepatocellular carcinoma (HCC), and 105 healthy controls. The polymerase chain reaction–restriction fragment length polymorphism strategy was used to detect ESR1 gene PvuII and XbaI polymorphisms.ResultsCompared with healthy controls, binary logistic regression analyses show that the CC genotype of PvuII was associated with a significantly increased susceptibility to CHB compared with the TT genotype (OR = 1.760, 95% CI 1.316–2.831; p = 0.044). The PvuII CC genotype was also associated with significantly increased risk of HBV-related LC (OR = 1.921, 95% CI 1.342–2.478; p = 0.043). Similarly, the subjects bearing the homozygous CC genotype of PvuII polymorphism also had more than a 1.7-fold increased risk for development of HCC (OR = 1.748, 95% CI 1.313–2.787; p = 0.010) compared with those bearing the TT genotype. Furthermore, the AC haplotype was associated with a significantly increased risk of HCC with an OR of 1.456 (p = 0.003). In contrast, there were no significant differences in the genotype and allele of XbaI polymorphisms in the ESR1 gene between the groups of patients and healthy controls. In addition, ESR1 polymorphisms were not significantly associated with susceptibility to HBV-related HCC when using CHB and LC patients as references.ConclusionWe conclude that the CC genotype of PvuII in ESR1 is associated with an increased risk of CHB, HBV-related LC and HCC in Guangxi Zhuang populations.     

Protective effects of HLA-DPA1/DPB1 variants against Hepatitis B virus infection in an Indonesian population

Human leukocyte antigen (HLA) DPA1/DPB1 variants have been reported to influence Hepatitis B virus (HBV) infection. HLA-DPA1/DPB1 plays a pivotal role in antigen presentation to CD4⁺ helper T cells and influences the outcome of HBV infection. To investigate the influence of HLA-DP variants on the outcome of HBV infection in an Indonesian population where it has the third-highest prevalence of HBV infection worldwide, we performed a case–control study of 686 participants, including patients with HBV-related advanced or nonadvanced liver disease, patients with spontaneously resolved HBV, and healthy controls. Single-nucleotide polymorphisms in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs228388) were genotyped using real-time TaqMan® genotyping assays. Because rs2281388 deviated from Hardy–Weinberg equilibrium, it was excluded from subsequent analyses. The results of logistic regression analyses showed that the HLA-DPB1 rs9277535 variants were associated with a reduced risk of persistent HBV infection (odds ratio [OR] 0.70, 95% confidence interval [95% CI] 0.52–0.96, P = 0.026, additive genetic model; OR 0.60, 95% CI 0.38–0.96, P = 0.033, dominant genetic model). The HLA-DPA1 rs3077 variant was associated with a protective effect increasing the spontaneously resolved HBV infection (OR 0.64, 95% CI 0.41–0.98, P = 0.039, dominant genetic model). By contrast, the HLA-DPB1 rs3135021 variant was not associated with the outcome of HBV infection, including susceptibility, spontaneously resolved, or disease progression. Combinations of haplotype markers were also associated with HBV susceptibility (CA for rs3077–rs9277535, OR 0.57, 95% CI 0.36–0.92, P = 0.021; GA for rs3135021–rs9277535, OR 0.56, 95% CI 0.36–0.86, P = 0.0087). In conclusion, these findings confirm that HLA-DPA1/DPB1 variants were associated with the outcomes of HBV infection in an Indonesian population.     

The effect of P2X7 receptor 1513 polymorphism on susceptibility to tuberculosis: A meta-analysis

Studies of the association between the purinergic receptor P2X, ligand-gated ion channel 7 (P2X7 receptor) gene 1513A/C polymorphism and susceptibility to tuberculosis have yielded inconsistent results. We performed this meta-analysis to help clarify these inconsistencies. After systematically searching PUBMED, MEDLINE, EMBASE and ISI Web of knowledge, two of the authors independently extracted relevant data and a meta-analysis was performed by using STATA11.0 software. A total number of nine studies involving 2195 cases and 2036 controls were identified. The results indicated that P2X7 receptor gene 1513C allele (OR 1.389, 95% CI 1.161–1.660, p < 0.001) and CC genotype (1.582, 95% CI 1.129–2.217, p = 0. 012) were significantly associated with increased susceptibility to tuberculosis. Subgroup analysis indicated that this SNP greatly contributed to susceptibility to tuberculosis in Asians. The C allele of P2X7 receptor gene 1513A/C polymorphism was also associated with increased susceptibility to pulmonary tuberculosis in Asians (C vs. A: OR 1.420, 95% CI 1.163–1.733, p = 0.001; (CC + AC) vs. AA: OR 1.522, 95% CI 1.186–1.953, p = 0.001). Greater association between P2X7 receptor gene 1513A/C polymorphism and susceptibility to extra-pulmonary tuberculosis with bigger ORs were found (C vs. A, OR 2.035, 95% CI 1.236–3.352, p = 0.005; CC vs. AA, OR 3.788, 95% CI 1.434–10.009, p = 0.007; AC vs. AA, OR 2.148, 95% CI 1.252–3.684, p = 0.005; (CC + AC) vs. AA, OR 2.386, 95% CI 1.302–4.374, p = 0.005; CC vs. (AC + AA), OR 2.692, 95% CI 1.242–5.836, p = 0. 012). This meta-analysis indicates that the C allele of P2X7 receptor gene 1513A/C polymorphism is a risk factor for pulmonary tuberculosis in Asians, while not in Africans or Latinos and a risk for extra-pulmonary tuberculosis. Further well-designed, large scale studies are required to confirm this conclusion.     

Genetic variants at 18q11.2 and 8q24 identified by genome-wide association studies were not associated with pulmonary tuberculosis risk in Chinese population

ObjectiveGenome-wide association study (GWAS) recently identified several susceptibility loci in ASAP1 gene on chromosome 8q24 for tuberculosis (TB) in a Russian population, but no relevant studies have been performed to validate these findings. In addition, previous GWAS in Ghana and Gambia found that the variant rs4331426 at 18q11.2 was a susceptibility locus for TB. However, the follow-up studies reported conflicting results. Herein, we investigated the contribution of genetic variants at 8q24 and 18q11.2 to TB in Chinese population.MethodsWe genotyped four genetic variants at 8q24 (rs10956514 and rs11774633) and 18q11.2 (rs4331426 and rs6507226) in a case–control study with 355 newly bacteriologically confirmed pulmonary TB cases and 395 healthy controls using TaqMan allelic discrimination assay. Subsequently, we conducted a meta-analysis including 4 reported studies in Chinese populations and our case–control study with a total of 3118 cases and 3226 controls to further evaluate the relationship between rs4331426 at 18q11.2 and TB risk.ResultsWe did not find significant association between genetic variants at 8q24 and risk of TB (rs10956514: OR = 0.89, 95%CI: 0.72–1.09, P = 0.253; rs11774633: OR = 0.86, 95%CI: 0.69–1.08, P = 0.206). We did not observe significant association for genetic variants at 18q11.2 (rs4331426: OR = 0.62, 95%CI: 0.34–1.14, P = 0.122; and rs6507226: OR = 0.98, 95%CI: 0.80–1.20, P = 0.853). Moreover, the pooled results from the Meta-analysis further supported that rs4331426 at 18q11.2 was not associated with TB risk in Chinese population (OR = 0.90, 95% CI: 0.63–1.29).ConclusionsOur findings indicate that TB risk-associated loci at 8q24 and 18q11.2 identified by GWAS from the other populations may not contribute to TB susceptibility in Chinese population.     

IFNL4 ss469415590 polymorphism contributes to treatment decisions in patients with chronic hepatitis C virus genotype 1b,but not 2a,infection

Recently, the dinucleotide variant ss469415590 (TT/ΔG) in a novel gene, interferon lambda 4 (IFNL4), was identified as a stronger predictor of hepatitis C virus (HCV) clearance in individuals of African ancestry compared with rs12979860. We aimed to determine whether this variant contributes to treatment decisions in a Chinese population. A total of 447 chronic hepatitis C (CHC) patients (including 328 treated with interferon alpha-2b and ribavirin), 129 individuals who had spontaneously cleared HCV (SHC), and 169 healthy controls were retrospectively investigated. ss469415590 genotyping was performed using a mass spectrometry method (SEQUENOM). A higher proportion of SHC individuals carried the TT/TT genotype compared with CHC patients (95.3% vs. 88.8%, P = 0.027). In patients with HCV genotype 1b, the ss469415590 variant was independently associated with sustained virologic response (SVR) (odds ratio [OR] = 3.247, 95% confidence interval [CI] = 1.038–10.159, P = 0.043) and on-treatment virological responses, including rapid (RVR), complete early (cEVR), early (EVR), and end-of-treatment (ETVR), with a minimal OR of 3.73. Especially for patients with high viral load (≥ 4 × 10⁵ IU/ml), ΔG allele carriers had a lower chance of achieving SVR compared with those carrying the TT/TT genotype (7.1% vs. 36.0%, P = 0.034, OR [95% CI] = 7.24 [1.02–318.45], negative predictive value = 92.9%). In patients with HCV genotype 2a, no significant association between the ss154949590 variant and the virological response was identified (P > 0.05). Additionally, we found that ss154949590 was in complete linkage disequilibrium with rs12979860. In conclusion, the IFNL4 ss154949590 TT/TT genotype favors spontaneous clearance of HCV. This same variant is associated with treatment-induced clearance in patients with genotype 1b, but not 2a. ss469415590 (or rs12979860) genotyping should be considered for patients with HCV genotype 1b and high viral load when making a choice between standard dual therapy and an IFN-free direct-acting antiviral regimen.     

Impacts of human leukocyte antigen DQ genetic polymorphisms and their interactions with hepatitis B virus mutations on the risks of viral persistence,liver cirrhosis,and hepatocellular carcinoma

Human leukocyte antigen (HLA)-DQ genetic polymorphisms have been associated with chronic hepatitis B virus (HBV) outcomes. We aimed to determine impacts of HLA-DQ polymorphisms and their interactions with HBV mutations on the risks of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). rs2856718 (A > G) and rs9275319 (A > G) were genotyped in 1342 healthy controls, 327 HBV surface antigen (HBsAg) seroclearance subjects, 611 asymptomatic HBsAg carriers (ASCs), 1144 chronic hepatitis B (CHB) patients, 734 LC patients, and 1531 HCC patients using quantitative PCR. HBV mutations were detected by direct sequencing. Logistic regression analyses were utilized to assess the factors and/or multiplicative interactions significantly associated with liver diseases. rs9275319 variant genotypes were inversely associated with HBV persistence compared to HBV natural clearance subjects. rs2856718 variant genotypes significantly increased LC risk compared to ASCs plus CHB patients (GG vs. AA: odds ratio [OR], 1.52, 95% confidence interval [CI], 1.17–1.97 and AG + GG vs. AA: OR, 1.27; 95% CI, 1.04–1.54) and decreased HCC risk compared to HCC-free HBV-infected subjects (AG vs. AA: OR, 0.76; 95% CI, 0.65–0.89 and AG + GG vs. AA: OR, 0.78, 95% CI, 0.68–0.90). rs2856718 variant genotypes were significantly associated with an increased frequency of HBV A1726C mutation, a LC-risk, HCC-protective mutation, in genotype C. A rs9275319 variant genotype (GG) was significantly associated with an increased frequency of preS1 start codon mutation, an HCC-risk mutation, in genotype C. The interaction of rs2856718 AG + GG genotype with T1753V, a HCC-risk mutation, significantly reduced LC risk, with an OR of 0.26 (95% CI, 0.09–0.78); whereas the interaction of rs2856718 AG genotype with C1673T, a LC-risk mutation, significantly increased HCC risk, with an OR of 2.80 (95% CI, 1.02–7.66) in genotype C HBV-infected subjects. Conclusively, the HLA-DQ polymorphisms affect the risks of LC and HCC differently in chronic HBV-infected subjects, possibly via interacting with the HBV mutations.     

Polymorphisms in the oligoadenylate synthetase gene cluster and its association with clinical outcomes of dengue virus infection

Oligoadenylate synthetases (OAS) play an important role in the immune response against dengue virus. Single nucleotide polymorphisms (SNPs) in the OAS genes are known to affect OAS activity and are associated with outcome of viral infections. Polymorphisms in the OAS1 (rs1131454 and rs10774671), OAS3 (rs2285932 and rs2072136) and OAS2 (rs15895 and rs1732778) genes were studied using PCR followed by restriction fragment length polymorphism methods in 109 patients hospitalized for dengue (DEN) and 105 healthy controls (HCs) who have no documented evidence of symptomatic dengue. The two locus haplotype of OAS2 G-G was significantly higher in all patient groups [DEN vs. HCs, P = 0.0041, P corrected (Pc) = 0.012, Odds ratio (OR) 1.73 95% CI 1.16–2.59] while the four locus haplotype of OAS3-OAS2 C-G-A-G was significantly lower in all dengue patient groups [DEN vs. HCs, P = 0.0054, Pc = 0.0486, OR 0.09, 95% CI 0.00–0.64] compared to controls. When the six locus haplotypes involving OAS1, OAS3 and OAS2 polymorphisms were analyzed and compared, the frequency of the haplotype A-A-C-A-G-G was significantly higher [P = 0.0267, Pc = 0.486, OR 2.34, 95% CI 1.08–4.91] and the frequency of the haplotype A-A-C-G-G-A was significantly lower in DHF cases [P = 0.014, Pc = 0.252, OR 0.12, 95% CI 0.01–0.85] compared to healthy controls. The results suggest that OAS1-OAS3-OAS2 haplotypes are associated with differential susceptibility to clinical outcomes of dengue infection.     

Association of the gene polymorphisms in sodium taurocholate cotransporting polypeptide with the outcomes of hepatitis B infection in Chinese Han population

ObjectiveIn recent years, sodium taurocholate cotransporting polypeptide (NTCP) was newly identified as a hepatitis B virus (HBV) receptor, which partly shed light on the reason for HBV hepatotropism and its host specificity. However, the related researches were limited to in vitro or animal experiments. Therefore, this study aimed to investigate the association of NTCP polymorphisms with HBV natural course in humans.MethodsAccording to their serological and clinical characteristics, 933 Chinese Han individuals were divided into two major groups, 352 viral clearance controls and 581 persistently infected patients. The latter one included 186 hepatocellular carcinoma (HCC) and 395 non-HCC subjects. A total of five single nucleotide polymorphisms (SNPs) were selected from HapMap dataset and genotyped by high resolution melting (HRM) curve method.ResultsThe rs7154439 AA genotype was observed slightly more common in viral clearance group than in persistently infected group [16 (4.5%) subjects vs. 10 (1.7%) subjects. p = 0.008, adjusted odds ratio (AOR) = 0.33, 95% confidence interval (CI) = 0.15–0.75 in a codominant model; and p = 0.006, AOR = 0.32, 95% CI = 0.14–0.72 in a recessive model]. While the rs4646287 AA genotype was observed slightly more frequent in HCC group than in non-HCC group [6 (3.2%) subjects vs. 1 (0.3%) subject. p = 0.018, AOR = 15.74, 95% CI = 1.59–155.54 in a codominant model; and p = 0.018, AOR = 15.91, 95% CI = 1.61–157.01 in a recessive model]. There were no statistically significant differences of allele or haplotype distribution between any two groups.ConclusionsThis study suggests that polymorphisms in the NTCP region may be associated with the natural course of HBV infection. The rs7154439 AA genotype was associated with HBV clearance, while the rs4646287 AA genotype was associated with HCC occurrence. However, considering the sample size is relatively small, larger studies, especially through multicenter collaboration will be needed to fully validate the significance of these findings.     

SFRP1 variations influence susceptibility and immune response to Mycobacterium tuberculosis in a Chinese Han population

ObjectivesSFRP1 acts as a well-established inhibitory regulator of the Wnt signaling pathway, whose polymorphisms have been demonstrated to be associated with the risk of inflammation, infection as well as cancer. We verified the hypothesis that single nucleotide polymorphisms (SNPs) within SFRP1 gene are associated with susceptibility and clinical characteristics of tuberculosis disease in a Chinese Han population.MethodsSix candidate SNPs were genotyped using MassARRAY method in a case–control design (260 tuberculosis patients and 252 healthy controls). A comprehensive analysis of single locus including the genotypic, allelic frequencies and the genetic models, haplotypic construction as well as gene–gene interaction was conducted to investigate the relationships between SNPs and TB. Significant SNPs were further interrogated in relation to TB clinical features and host inflammatory status.ResultsGenotype frequencies of rs4736958 and rs7832767 within SFRP1 gene were significantly different (p = 0.011, p = 0.008, respectively) between tuberculosis group and control group. Subjects carrying C allele for rs4736958 showed a decreased tuberculosis risk (OR = 0.66, 95% CI = 0.51–0.87, p = 0.003), whereas individuals carrying rs7832767 T allele had a significant increased risk in tuberculosis susceptibility (OR = 1.32, 95% CI = 1.01–1.74, p = 0.046). Genetic model analysis revealed that dominant, co-dominant and recessive models of rs4736958 were associated with decreased susceptibility to tuberculosis (p all < 0.05), while the recessive and co-dominant models of rs7832767 were related to significantly increased risk for tuberculosis (p all < 0.05). There was a reduced tuberculosis risk in association with the haplotype CC (representing rs3242 and rs4736958) of SFRP1 (OR = 0.73, 95% CI = 0.56–0.96, p = 0.026). Further stratification analysis indicated that TB patients with genotype CT for rs4736958 were associated with higher CRP concentrations, and heterozygous patients (CT genotype) of rs7832767 trended towards greater ESR levels.ConclusionSNPs rs4736958 and rs7832767 of SFRP1 gene were significantly associated with tuberculosis susceptibility and might influence the expression levels of inflammatory markers of tuberculosis patients in a Chinese Han population.     

The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: A meta-analysis

BackgroundAlthough there have been previous studies on the potential association between cytochrome P450 2E1 (CYP2E1) polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH), the results have generally been controversial.MethodsWe searched Medline/PubMed, EMBASE, Web of Science, and the Cochrane Library using the following key words: cytochrome P450 2E1, CYP2E1, polymorphism, tuberculosis and TB. The strength of the association between the CYP2E1 PstI/RsaI and DraI polymorphism and ATDH risk as measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied.ResultsCompared with the wild genotype (c1/c1), the OR of ATDH was 1.41 (95% CI: 1.1–1.82, P = 0.007) for the PstI/RsaI polymorphism, and 0.78 (95% CI: 0.51–1.18, P = 0.23) for the DraI polymorphism. Compared with individuals with N-acetyltransferase 2 (NAT2) fast or intermediate acetylator genotype and c1/c1 genotype patients who were NAT2 slow acetylators and carried the high activity CYP2E1 c1/c1 genotype had higher risk for ATDH (OR = 3.10, P < 0.0001).ConclusionThe present meta-analysis indicates that the CYP2E1 c1/c1 genotype may be a risk factor for ATDH, and the concomitant presence of the slow acetylator NAT2 genotype may further increase this risk.     

Joint effects of objectively-measured sedentary time and physical activity on all-cause mortality

ObjectiveExamine the joint effects of objectively-measured sedentary time and moderate-to-vigorous physical activity (MVPA) on all-cause mortality.MethodsThe present study included data from the 2003–2006 National Health & Nutrition Examination Survey, with mortality follow-up data (via National Death Index) through 2011 (N = 5575 U.S. adults). Sedentary time (activity counts/min between 0 and 99) and MVPA (activity counts/min ≥ 2020) were objectively measured using the ActiGraph 7164 accelerometer.ResultsThe median age of the participants was 50 yrs; proportion of men was 50.2%; proportion of whites was 53.8%, 18.7% for blacks; median follow-up was 81 months; and 511 deaths occurred over the follow-up period. After adjusting for age, gender, race-ethnicity, cotinine, weight status, poverty level, C-reactive protein and comorbid illness (summed score of 0–8 chronic diseases), and for a 1 min increase in MVPA and sedentary time, both MVPA (HR_adjusted = 0.98; 95% CI: 0.96–0.99; P = 0.04) and sedentary time (HR_adjusted = 1.001; 95% CI: 1.0003–1.002; P = 0.008) were independently associated with all-cause mortality. Further, MVPA was associated with all-cause mortality among those with greater (above median) sedentary time (HR_adjusted = 0.95; 95% CI: 0.93–0.97; P < .001). Sedentary time was not associated with all-cause mortality among those engaging in above median levels of MVPA (HR_adjusted = 0.998; 95% CI: 0.996–1.001; P = .32), but sedentary time was associated with increased mortality risk among those below median levels of MVPA (HR = 1.002; 95% CI: 1.001–1.003; P < 0.001).ConclusionsSedentary time and MVPA are independently associated with all-cause mortality. Above median sedentary time levels did not negate the beneficial effects of MVPA on all-cause mortality risk.     

Polymorphisms in the prostaglandin receptor EP2 gene confers susceptibility to tuberculosis

ObjectivesProstaglandin E2 (PGE2) is an important lipid mediator of the inflammatory immune response during acute and chronic infections. PGE2 modulates a variety of immune functions via four receptors (EP1–EP4), which mediate distinct PGE2 effects. Mice lacking EP2 are more susceptible to infection by Mycobacterium tuberculosis (M.tb), have a higher bacterial load, and increase size and number of granulomatous lesions. Our aim was to assess whether single nucleotide polymorphisms (SNPs) in EP2 increase the risk of tuberculosis.MethodsDNA re-sequencing revealed five common EP2 variants in the Chinese Han population. We sequenced the EP2 gene from 600 patients and 572 healthy controls to measure SNP frequencies in association with tuberculosis infections (TB) within the population.ResultsThe rs937337 polymorphism is associated with increased risk to tuberculosis (p = 0.0044, odds ratio [OR], 1.67; 95% confidential interval,1.22–2.27). The rs937337 AA genotype and the rs1042618 CC genotype were significantly associated with TB. An estimation of the frequencies of haplotypes revealed a single protective haplotype GACGC for tuberculosis (p = 0.00096, odds ratio [OR], 0.56; 95% confidential interval, 0.41–0.77). Furthermore, we determined that the remaining SNPs of EP2 were nominally associated with clinical patterns of disease.ConclusionsWe identified genetic polymorphisms in EP2 associated with susceptibility to tuberculosis within a Chinese population. Our data support that EP2 SNPs are genetic predispositions of increased susceptibility to TB and to different clinical patterns of disease.     

Toll-like receptor 1 and 10 polymorphisms,Helicobacter pylori susceptibility and risk of gastric lesions in a high-risk Chinese population

Genetic polymorphisms of Toll-like receptor (TLR) 1 and 10 may influence Helicobacter pylori (H. pylori) susceptibility. To evaluate associations between TLR1 and 10 polymorphisms, H. pylori infection, and precancerous gastric lesions, a population-based study was conducted in a high-risk Chinese population.Three single-nucleotide polymorphisms, TLR1 rs4833095, TLR10 rs10004195, and TLR10 rs4129009 were genotyped by TaqMan SNP genotyping assay in 2553 participants with diverse gastric lesions. The status of H. pylori infection was determined by ¹³C-urea breath test.TLR1 rs4833095 T and TLR10 rs10004195 T alleles were the minor alleles and showed in linkage disequilibrium (D′ = 0.98, r² = 0.73) in the Chinese population. A decreased risk of H. pylori infection was observed in subjects with TLR1 rs4833095 CT genotype [adjusted odds ratio (OR) = 0.80; 95% confidence interval (CI): 0.66–0.96] or T allele (OR = 0.82; 95%CI: 0.69–0.99). Moreover, subjects carrying TLR1 rs4833095 TT genotype were associated with reduced risks of chronic atrophic gastritis (CAG, OR = 0.66; 95%CI: 0.45–0.97) and intestinal metaplasia (IM, OR = 0.57; 95%CI: 0.36–0.90). The risk of CAG was also decreased in subjects carrying TLR10 rs10004195 T allele (OR = 0.75; 95%CI: 0.57–0.99). Furthermore, haplotype analysis indicated that haplotype TT of rs4833095 and rs10004195 had a protective effect on H. pylori infection (OR = 0.83; 95%CI: 0.72–0.96) or precancerous gastric lesions (OR = 0.78; 95%CI: 0.64–0.96 for CAG, and OR = 0.74; 95%CI: 0.57–0.96 for IM).These findings suggest that TLR1 rs4833095 and TLR10 rs10004195 may play crucial roles in H. pylori susceptibility and gastric pathogenesis.     

Association between SNPs in miRNA-machinery genes and chronic hepatitis B in the Chinese Han population

Single nucleotide polymorphisms (SNPs) in miRNA-machinery genes can influence their generation and maturation, then expression and structure. To explore the relationship between three SNPs (rs3757 in DGCR8, rs636832 in AGO1, rs7813 in GEMIN4) in miRNA-machinery genes and chronic hepatitis B, we genotyped the SNPs by high resolution melting method (HRM) in a case-control study of 332 unrelated chronic hepatitis B patients and 352 unrelated healthy controls in Western China. Interestingly, the rs636832 was significantly associated with the susceptibility of CHB (genotype: AA/GA/GG: p = 0.010; allele: A/G: OR = 0.727, 95% CI = 0.575–0.920, p = 0.008). The minor allele A of rs636832 was significantly associated with a decreased risk of CHB. Additionally, the dominant model AG + GG vs. AA showed a risk of 1.442-fold (p = 0.018) with CHB. Further exploration for the association between rs636832 and HBV-DNA load in 329 cases showed no significant difference (genotype: p = 0.321; allele: p = 0.148). Neither did the association between rs636832 and the status of HBsAg and HbeAg (HBsAg: genotype p = 0.337, allele p = 0.436; HBeAg: genotype p = 0.861, allele p = 0.822). Our study first provided the evidence that rs636832 in AGO1 was associated with chronic HBV infection susceptibility in Chinese Han population. Further epidemiological and functional studies in larger populations are warranted to verify our results.     

Inadequate diabetes knowledge is associated with poor glycemia control in patients with type 2 diabetes

ObjectiveTo identify the association between glycemia control with level of diabetes knowledge, diabetes education, and lifestyle variables in patients with type 2 diabetes.DesignCross-sectional analytical study.SiteClinics of the Mexican Institute of Social Security (IMSS), Mexico.ParticipantsPatients with type 2 diabetes.Main measurementsGlycated hemoglobin (HbA1c), glucose, and lipid profile levels were measured from fasting venous blood samples. Assessment of disease knowledge was performed using the Diabetes Knowledge Questionnaire (DKQ-24). Systolic and diastolic blood pressure was measured. Weight and abdominal circumference were measured, as well as body composition using bioimpedance. Sociodemographic, clinical, and lifestyle variables were obtained.ResultsA total of 297 patients were included, sixty-seven percent (67%) were women with a median of six years since the diagnosis of diabetes. Only 7% of patients had adequate diabetes knowledge, and 56% had regular knowledge. Patients with adequate diabetes knowledge had a lower body mass index (p = 0.016), lower percentage of fat (p = 0.008), and lower fat mass (p = 0.018); followed a diet (p = 0.004) and had received diabetes education (p = 0.002), and to obtain information about their illness (p = 0.001). Patients with low levels of diabetes knowledge had a higher risk of HbA1c ≥ 7% (OR: 4.68; 95% CI: 1.48,14.86; p = 0.009), as well as those who did not receive diabetes education (OR: 2.17; 95% CI: 1.21–3.90; p = 0.009) and those who did not follow a diet (OR: 2.37; 95% CI: 1.01,5.55; p = 0.046).ConclusionInadequate knowledge of diabetes, lack of diabetes education, and dietary adherence are associated with poor glycemia control in patients with diabetes.     

The MTHFR C677T mutation is not a risk factor recognized for HBV-related HCC in a population with a high prevalence of this genetic marker

BackgroundPolymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene can affect disease progression in HBV infection. However, the results from different reports are inconsistent. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and the outcome of HBV infection in a Tianjin Han population.MethodsTaqMan SNP genotyping was employed to determine the alleles and genotypes of MTHFR C677T in 2511 subjects from various stages of HBV infection and 549 healthy controls.ResultsOf the 3060 subjects, the genotypic frequencies were CT 48.9%, TT 29.3% and CC 21.8%; the allelic frequencies were T 53.8% and C 46.2%. There was no significant difference in genotypic or allelic distribution among the different disease groups. When either healthy subjects or self-limited subjects were used as controls, the TT genotype and the T allele conferred protective effects against hepatocellular carcinoma (HCC) (HCC vs healthy subjects: OR = 0.588, 95% CI = 0.413–0.836, P = 0.003; OR = 0.768, 95% CI = 0.645–0.915, P = 0.003, respectively. HCC vs self-limited subjects: OR = 0.598, 95% CI = 0.404–0.886, P = 0.010; OR = 0.772, 95% CI = 0.635–0.940, P = 0.010, respectively). After sub-stratification by gender, the prevalence of the TT genotype or T allele was the lowest in the male HCC group (TT 23.5%, T 49.8%). The protective effects of the TT genotype and the T allele were observed in male HCC and cirrhotic subjects (HCC vs self-limited subjects: OR = 0.470, 95% CI = 0.288–0.766, P = 0.002; OR = 0.681, 95% CI = 0.535–0.866, P = 0.002, respectively. Liver cirrhosis vs self-limited subjects: OR = 0.624, 95% CI = 0.392–0.992, P = 0.046; OR = 0.791, 95% CI = 0.627–0.998, P = 0.048, respectively), but not in female. When the subjects were stratified according to the clinical features, no statistically significant difference in the genotypic distribution was observed (P > 0.05).ConclusionsThe TT genotype and T allele of MTHFR C677T may confer a protective effect on disease progression to HCC in HBV-infected individuals, especially among male patients, in a population with a high prevalence of this genetic marker.     

Association of promoter region polymorphisms of CD209 gene with clinical outcomes of dengue virus infection in Western India

Dendritic cell specific intercellular adhesion molecule 3 grabbing non-integrin, coded by the CD209 gene, acts as an entry receptor for dengue virus. Polymorphisms in the promoter region of CD209 gene (rs735239, rs4804803, rs2287886) were investigated in 112 hospitalized cases of dengue (DEN) and 104 healthy controls to find out whether they are associated with dengue in a Western Indian population. Results revealed a significantly higher frequency of ‘G’ allele and ‘G/G’ genotype of rs2287886 and A-A-G haplotype of CD209 gene in DEN compared to healthy controls [For ‘G/G’ genotype, P = 0.0072, Odds ratio (OR) 2.43; For A-A-G haplotype, P = 0.0033, OR 2]. The frequency of A/A genotype of rs735239 was higher in DEN cases with thrombocytopenia compared to cases without thrombocytopenia (P = 0.026). The results suggest that rs2287886 G/G genotype of CD209 gene is associated with development of dengue requiring hospitalization while A/A genotype of rs735239 is associated with thrombocytopenia in dengue cases.     

The polymorphisms of MSH6 gene are associated with AIDS progression in a northern Chinese population

It has been reported that DNA repair genes play an important role in HIV-1 infection and AIDS progression. One DNA repair pathway, the mismatch repair (MMR) is associated with a wide variety of tumors. However, the role of single nucleotide polymorphisms (SNPs) in the MMR genes and their importance in HIV-1 infection and AIDS progression remain unclear. In the present study, 479 HIV-1-infected and 487 healthy individuals from northern China were genotyped for nine SNPs in the MSH2 gene (rs13019654, rs4608577, rs4952887, rs6726691, rs10191478, rs12999145, rs1981929, rs2042649, rs2303428) and five SNPs in the MSH6 gene (rs2348244, rs3136245, rs3136329, rs2072447, rs7562048). Our results showed that the rs7562048 G allele frequency was significantly higher in the cases with the CD4⁺ T-lymphocyte count < 200 cells/μl than those with > 200 cells/μl (P = 0.001, OR = 1.811, 95% CI 1.255–2.614), which is in agreement with the result of the Bonferroni correction. The frequencies of the rs2348244 C allele and rs3136245 T allele were higher in the cases at clinical phase IV than those at clinical phase I + II + III (P = 0.026, OR = 1.591, 95% CI 1.056–2.398 and P = 0.019, OR = 1.749, 95% CI 1.096–2.791, respectively); however, this difference is not supported by the Bonferroni correction. There were no significant differences in the frequency of allele, genotype and haplotype of the 14 SNPs between HIV-1-infected individuals and healthy controls (P > 0.05). These results suggest that the rs7562048 is associated with the clinical features and that the MSH6 gene polymorphisms likely play an important role in the progression of AIDS in the northern Chinese population.     

Association of genetic polymorphisms in CD8 + T cell inhibitory genes and susceptibility to and progression of chronic HBV infection

BackgroundPrevious studies have shown that multiple inhibitory genes play an important role in HBV-specific CD8 + T cell exhaustion and dysfunction in the setting of chronic HBV infection. Polymorphic variants of these genes are thought to be predisposing factors for HBV susceptibility, clearance, and disease progression. The aim of this retrospective study was to identify variants affecting chronic HBV infection in a Chinese Han population.MethodsWe chose 28 tgSNPs from HapMap data on 5 key genes. They were genotyped on a total of 858 chronic HBV patients, 429 patients who underwent spontaneous recovery, and 239 healthy controls. We evaluated the correlation between the polymorphisms and HBV susceptibility, spontaneous clearance, and disease progression.ResultsThe association of rs3827537 of BIM genotype TA and allele A was significantly different (P = 0.016, OR = 2.049; P = 0.031, OR = 1.925) between HBV patients and healthy controls. The rs36084323 of PD-1, as well as rs3766377, rs485618, rs4656942 of CD244 showed significant associations with the risk for HBV-related cirrhosis and hepatocellular carcinoma (HCC) (P = 0.009, OR = 0.482; P = 0.009, OR = 4.573; P = 0.015, OR = 0.580; P = 0.028, OR = 2.855). MDR analysis revealed that the four SNPs (rs36084323, rs3766377, rs485618, rs4656942) modulated the predisposition to cirrhosis and HCC in patients with chronic HBV infection (P = 0.006). Using a luciferase reporter assay, we demonstrated that various alleles of rs3766377 had differential effects, and rs3766377 and rs485618 might have interactive effects.ConclusionsThe present study reveals genetic associations among PD-1 and CD244 variants that may be involved in the development of cirrhosis and HCC in patients with chronic HBV infection. The BIM variant was associated with HBV susceptibility.     

Treatment with PEG-IFN and ribavirin in patients with chronic hepatitis C,low grade of hepatic fibrosis,genotype 1 and 4 and favorable IFNL3 genotype: A pharmacogenetic prospective study

The new direct-acting antivirals agents (DAAs) rapidly changed the treatment approach in chronic hepatitis C (CHC); however, the interferon (IFN)-free therapies availability is currently different in some countries, due to higher costs of these drugs. Naïve treated patients, who are not eligible for IFN-free therapies, could be selected for standard dual treatment with pegylated (PEG)-IFN and ribavirin (RBV), through IFN lambda 3 gene polymorphisms and fibrosis stage evaluation.Inclusion criteria were: naïve treated CHC patients with GT1 or GT4, without major contraindication to PEG-IFN or RBV, with fibrosis stage F0-F2 and IFNL3 rs8099917/rs12979860 TT/CC genotypes.65 patients were included in the study. Overall SVR was observed in 50 patients (76.9%); SVR rates among different genotypes were as follows: 15 with GT1a (71.4%), 27 with GT1b (79.4%) and 8 for GT4 (80%). The RBV cutoff at 2 weeks of 1800 ng/mL, predictor of RVR, was determined (p = 0.003; sensibility = 60.4%, specificity = 88.2%, positive predictive value = 88.9%, negative predictive value = 100%). In multivariate analysis, factors significantly associated with treatment failure were living alone condition (OR = 4.302; 95%IC = 1.254–16.257; p = 0.034) and RBV plasma level < 1800 ng/mL at 2 weeks (OR = 4.970; 95%IC = 1.405–17.565; p = 0.009).Considering a pharmacogenetic-guided approach, dual therapy with PEG-IFN and RBV can be considered a reliable option for patients ineligible for IFN-free treatments, who are motivated and well informed about all the aspects related to PEG-IFN administration.