FcγRIIa and FcγRIIIb polymorphisms and associations with clinical manifestations in systemic lupus erythematosus patients

Abstract

In this study, we aimed to investigate whether the distribution of the FcγRIIa and FcγRIIIb polymorphisms determines susceptibility to systemic lupus erythematosus (SLE) and acts as predictors of SLE clinical manifestations in the Brazilian patients. A total of 157 patients that fulfilled the American College of Rheumatology classification criteria for SLE and 160 healthy volunteers were included in this study. FCGR2A and FCGR3B genotypes were determined by polymerase chain reaction-based allotyping methods with allele-specific primers; the clinical features were obtained from the patients' official medical records. In the case of FcγRIIa polymorphism, it was observed association of the allele FCGR2A-R-131 (p?=?0.02, odds ratio (OR)=1.44) and genotype RR-131 (p?=?0.03, OR?=?2.09) with SLE. These associations were higher with allele (p?<?0.01, OR?=?1.67) as well genotype (p?=?0.01, OR?=?2.85) when lupus nephritis was considered. In contrast, the allele FCGR2A-H-131 was associated with susceptibility to arthritis and anti-DNA antibodies (p?=?0.05 for both). As for FcγRIIIb polymorphism, skewing did not differ significantly between patients and controls, however the genotype FCGR3B*02*02 was associated with susceptibility to arthritis (p?=?0.02) and malar rash (p?=?0.03), but no association with nephritis was found. The results demonstrate that FcγRIIa polymorphism is associated with susceptibility to SLE in Brazilian patients, whereas for FcγRIIIb polymorphism no association was found. However, notably, both polymorphisms present allelic variants that influence the clinical manifestations and may contribute to the pathogenesis of the disease. In addition, to our knowledge, this is the first study considering the frequency of FcγRIIIb polymorphism in Brazilian SLE patients.     

Association study of interleukin-19 rs2243188 polymorphism with systemic lupus erythematosus in a Chinese population

Abstract

The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP), rs2243188 of interleukin-19 (IL-19), show significant evidence for association with SLE in a Chinese population. A total of 545 SLE patients and 613 healthy controls were collected in the present study. The genotyping of IL-19 rs2243188 polymorphism was detected by TaqMan allele discrimination assay on the 7300 real time polymorphism chain reaction system. The minor C allele of rs2243188, relative to the major A allele, appeared to have a significantly lower frequency in SLE patients (31.0%) as compared with controls (35.5%) (χ²?=?5.19, p?=?0.023). We also discovered a statistical significance in the dominant model (CC?+?CA versus AA: OR?=?0.755, 95% CI?=?0.598–0.953, p?=?0.018). However, no significant difference in genotype distribution was found between SLE patients and controls (p?=?0.056). Furthermore, an increased frequency of CC genotype were also detected in lupus nephritis (LN) groups as compared with non-LN groups (p?=?0.024). Besides, the individuals with CC genotype had a 2.201-fold higher risk for the susceptibility to LN than those A allele carriers (AA?+?CA) (p?=?0.006). Unfortunately, the analyses on the relationship of IL-19 rs2243188 with several clinical manifestations of SLE failed to find any significant results. In conclusion, our observations suggested the minor C allele of SNP rs2243188 might be a protective factor for SLE in a Chinese Han population. Moreover, the subgroup analysis highlighted that IL-19 rs2243188 SNP was associated with the susceptibility to LN patients.     

Study on influence of age,gender and genetic variants on lactose intolerance and its impact on milk intake in adult Asian Indians

Background: Lactase non-persistence (LNP) has been associated with the CC genotype of ?13910C?>?T and GG genotype of ?22018G?>?A polymorphisms present upstream of the lactase gene. Lactose intolerance (LI) is caused when gastrointestinal symptoms develop in individuals with low lactase activity.

Objective: To analyse association of LNP genotype and LI symptoms with milk intake and determine whether factors such as age, gender and genotype affect LI status.

Subjects and methods: Genetic analysis and lactose tolerance test (LTT) were performed on 205 healthy Indian adults. The pattern of milk consumption was recorded using a dietary questionnaire.

Results: LI was strongly associated with ?13910CC genotype (OR?=?10.28, 95% CI?=?2.32–45.55, p?=?0.002). Females were found to be at a higher risk of developing LI (OR?=?2.47, 95% CI?=?1.33–4.59, p?=?0.004). The association of the ≥50 years age group with LI was marginally significant (OR?=?1.86, 95% CI?=?0.995–3.47, p?=?0.05). Frequency and quantity of milk intake were lower in subjects belonging to the LNP genotype and LI groups (p?Conclusions: Subject study suggests that gender and genotype may be associated with development of LI. Association of age with LI was marginal. The data also indicate that LNP genotype and LI may play a role in influencing milk intake in individuals.     

Influence of HumDN1 VNTR polymorphism on DNASE1 expression in systemic lupus erythematosus and rheumatoid arthritis

The purpose of this study was to analyze the effect of the HumDN1 VNTR polymorphism on DNASE1 mRNA expression and enzyme activity in lupus (SLE) and rheumatoid arthritis (RA) compared to healthy control (HC). Kuwait subjects (n?=?500) matched by age/gender/ethnicity were genotyped by fragment-analysis. DNASE1 expression was analysed using quantitative Real-Time-PCR and sera from subjects were screened for DNase1 reduction activity by ELISA. Allele and genotype distribution of HumDN1 VNTR revealed a significant association with susceptibility to SLE and RA (p?<?0.05, OR?>?1). Relative expression analysis revealed a significant increase in DNASE1 mRNA in SLE (p?=?0.0001) and RA (p?=?0.002) compared to HC. Stratification of subjects revealed, increased DNASE1 expression in SLE with 5/5 (p?=?0.0001), 3/4 (p?=?0.0001) and 3/5 genotype (p?=?0.01). A reduction in DNASE1 expression was specifically observed in SLE with 4,4 genotype (p?=?0.0004). RA patients with 3/4 genotype (p?=?0.02) showed a significant increase in DNASE1 expression. Similarly a significant association was observed between DNase1 reduction activity and SLE (p?=?0.0001). SLE patients with 3,4 (p?=?0.0001) and 5,5 genotype (p?=?0.0001) showed increased DNase1 reduction activity, while a lack of association was observed with RA. The present study is the first to reveal the effect of HumDN1 VNTR on DNASE1 expression in SLE and RA.     

PTPN22 1858C > T polymorphism and susceptibility to systemic lupus erythematosus: a meta-analysis update

Studies performed in the past years showed PTNP22 1858?C?>?T (rs2476601) polymorphism as associated with systemic lupus erythematosus susceptibility, although conflicting findings are still found. In this context, a powerful statistical study, such as meta-analysis, is necessary to establish a consensus. The aim of this study was to evaluate association studies between the PTPN22 1858?C?>?T polymorphism and SLE by a meta-analysis update, including three recently published studies in the last three?years. A total of 3868 SLE patients and 7458 healthy individuals were considered herein, enclosing 19 studies from Asian, American, European and Latin ethnic groups. Odds ratio (OR) was performed for allelic, dominant and recessive genetic models. Statistically significant association was found between the PTPN22 1858?C?>?T polymorphism and susceptibility to SLE in all inheritance models. Allelic genetic model data (OR?=?1.54, 95% confidence interval (CI)?=?1.38–1.72, p value=.000) shows that T allele confers increased SLE susceptibility. As well as recessive genetic model (OR?=?2.04, 95% CI?=?1.09–3.82, p value?=?.030) for T/T genotype. Instead, dominant genetic model shows that C/C genotype confers lower susceptibility for SLE development (OR?=?0.62, 95% CI?=?0.54–0.72, p value?=?.000). In addition, we provided an ethnicity-derived meta-analysis. The results showed association in Caucasian (OR?=?1.47, p value?=?.000) and Latin (OR?=?2.41, p value?=?.000) ethnic groups. However, rs2476601 polymorphism is not associated nor in Asian (OR=?1.31; p value?=?.54) and African (OR?=?2.04; p value=.22) populations. In conclusion, present meta-analysis update confirms that T allele and T/T genotype in PTPN22 1858?C?>?T polymorphism confers SLE susceptibility, particular in Caucasian and Latin groups, suggesting PTPN22 1858?C?>?T as a potential genetic marker in SLE susceptibility.     

The −675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus,its clinical manifestations,and comorbidities in Mexican-Mestizo population

Abstract

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the ?675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the ?675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The ?675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81–3.87; p?<?.001) and 4G/4G (OR = 2.70; CI 1.62–4.51; p?<?.001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31–2.03; p?<?.001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84–3.84; p?<?.001). The 4G/5G genotype was associated with shorter disease duration (p?=?.039), as well as lower levels of haemoglobin (p?=?.001) and haematocrit (p?=?.009); the need for prednisone treatment (p?=?.001), higher BMI (p?=?.03), presence of type 2?DM (p?=?.015), clinical activity (Mex-SLEDAI = 57%; p?=?.047), Chronicity (SLICC-ACR = 0; p?=?.015) and CRP levels (p?=?.015) were associated with 5G/5G genotypes. In conclusion, the ?675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.     

Emerging Role of SIGIRR rs7396562(T/G) Polymorphism in Systemic Lupus Erythematosus in a Chinese Population

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, with heterogeneous presentation. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs7396562, of the interferon induced with single immunoglobulin IL-1-related receptor (SIGIRR) gene with SLE in a Chinese population. A total of 741 SLE patients and 731 healthy control subjects were enrolled in the present study. The genotyping of polymorphism (rs7396562) was determined by TaqMan allele discrimination assay on the 7,300 real-time polymerase chain reaction system. The frequency of T allele for rs7396562 in patients was significantly higher than in controls (T versus G, OR?=?1.318, 95 % confidence interval (CI)?=?1.139–1.525, P?P?versus GG, P?=?0.002; TT versus TG?+?GG, P?=?0.002). We also analyzed the association of the SIGIRR rs7396562 T allele with clinical features; luckily, photosensitivity and malar rash had some significant signal with the SNP. In conclusion, our study represents the first report demonstrating an association of the SIGIRR rs7396562 polymorphism with SLE susceptibility in a Chinese population.     

Meta-Analysis: The Relationship Between CTLA-4 +49 A/G Polymorphism and Primary Biliary Cirrhosis and Type I Autoimmune Hepatitis

Objectives: CTLA-4 exon-1 +49A?>?G (rs231775) polymorphism has been reported to influence the risk for primary biliary cirrhosis (PBC) as well as type I autoimmune hepatitis (AIH-1) in many studies; however, the results still remain controversial and ambiguous. This study aimed to determine more precise estimations for the relationship between CTLA-4 +49 A?>?G polymorphism and the risk for PBC and AIH-1 by using a meta-analysis.

Design and Methods: PubMed, EMBASE and MEDLINE were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.

Results: Fifteen studies including 3661 patients with PBC and 4427 controls as well as seven studies including 1270 patients with AIH-1 and 1614 controls were identified. Our pooled analysis revealed that G allele of CTLA-4 gene +49A/G polymorphism may confer an increased risk of PBC in overall (p?=?0.001, OR?=?1.29; 95% CI?=?1.13–1.47) and Caucasians (p?=?0.001, OR?=?1.32; 95% CI?=?1.21–1.44). At genotypic level, the codominant, dominant and recessive models showed no significant association with PBC. With respect to AIH-1, the AG genotype demonstrated a trend for association with increased risk of AIH-1 (p?=?0.04, AG vs. AA, OR?=?1.20; 95% CI?=?1.01–1.43). However, the CTLA-4 alleles as well as genotypes in dominant and recessive models were not associated with a risk for AIH-1 in both Caucasians and Asians.

Conclusions: This meta-analysis concluded that the CTLA-4 G allele and the AG genotype were associated with an increased risk for PBC and AIH-1, respectively, suggesting the CTLA-4 +49 A/G polymorphism as a candidate of susceptibility locus to PBC and AIH-1.     

Interaction analysis between BLK rs13277113 polymorphism and BANK1 rs3733197 polymorphism,MMEL1/TNFRSF14 rs3890745 polymorphism in determining susceptibility to rheumatoid arthritis

Two pairwise genetic interactions (B cell lymphocyte kinase (BLK) rs13277113,B cell scaffold protein with ankyrin repeats 1 (BANK1) rs3733197and BLK rs13277113 membrane metalloendopeptidase like 1 (MMEL1)/ tumor necrosis factor receptor superfamily member 14 (TNFRSF14) rs3890745) have been demonstrated in determining susceptibility to rheumatoid arthritis (RA) without replication, thus this study was performed to examine whether abovementioned genetic polymorphisms were associated with RA and further tests were performed to see whether aforementioned genetic interactions existed in RA among Chinese population. A total of 328 patients with RA and 449 healthy control subjects were included in the current study. The polymorphisms were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. The association of RA with each polymorphism was analyzed by multivariate logistic regression model. Interaction analysis was done by multiple methods. Significant difference in genotype distribution of BLK rs13277113 polymorphism between RA patients and healthy controls was found (p?=?1.01?×?10^?2). The major allele A of BLK rs13277113 polymorphism was significantly increased in RA patients compared with controls (OR?=?1.36, 95% CI?=?1.08–1.71, p?=?9.27?×?10^?3). Significant association of RA with the major allele A of BLK rs13277113 polymorphism under dominant model was also detected (OR?=?2.74, 95% CI?=?1.42–5.29, p?=?2.73?×?10^?3). However, we did not find significant association between neither BANK1 rs3733197 polymorphism nor MMEL1/TNFRSF14 rs3890745 polymorphism and RA. Non-significant evidence was found for neither additive nor multiplicative interaction for these two pairwise genetic polymorphisms (BLK rs13277113-BANK1 rs3733197; BLK rs13277113-MMEL1/TNFRSF14 rs3890745). Significant association of RA with G allele of BANK1 rs3733197 polymorphism was only found among individuals carrying A/A genotype of the BLK rs13277113 polymorphism (OR?=?1.49, 95% CI?=?1.01–2.18, p?=?.04). In summary, our results indicated that the BLK rs13277113 polymorphism was involved in the genetic background of RA in Chinese population and the association of BANK1 rs3733197 polymorphism with RA was dependent on the genotype of BLK rs13277113 polymorphism, highlighting B-cell response implicated in the pathogenesis of RA.     

Association Study of Common Genetic Variants in Pre-microRNAs in Patients with Ulcerative Colitis

Background

Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population.

Methods

The rs11614913 (T?>?C), rs2910164 (C?>?G), and rs3746444 (A?>?G) SNPs were genotyped in 170 UC and 403 control subjects.

Results

The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR)?=?1.51, 95% CI?=?1.03?C2.21, p?=?0.037). The rs3746444 AG genotype was associated with onset at an older age (OR?=?1.70, 95% CI?=?1.04?C2.78, p?=?0.035), left-sided colitis and pancolitis (left-sided colitis, OR?=?2.10, 95% CI?=?1.12?C3.94, p?=?0.024; pancolitis, OR?=?1.81, 95% CI?=?1.09?C3.01, p?=?0.028, left-sided colitis?+?pancolitis, OR?=?1.91, 95% CI?=?1.26?C2.92, p?=?0.003), higher number of times hospitalized (OR?=?2.63, 95% CI?=?1.22?C5.69, p?=?0.017), steroid dependence (OR?=?2.63, 95% CI?=?1.27?C5.44, p?=?0.014), and refractory phenotypes (OR?=?2.76, 95% CI?=?1.46?C5.21, p?=?0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2??, OR?=?0.36, 95% CI?=?0.17?C0.79, p?=?0.012), steroid dependence (OR?=?0.42, 95% CI?=?0.21?C0.88, p?=?0.021), and refractory phenotypes (OR?=?0.38, 95% CI?=?0.20?C0.72, p?=?0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C?+?C/C, OR?=?2.21, 95% CI?=?1.17?C4.18, p?=?0.016).

Conclusions

Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.     

Association between Q192R paraoxonase 1 polymorphism and serumadipocyte-fatty acid binding protein (FABP4) levels in Mexican women

Aim: This study aimed to evaluate the genetic effects of PON1 Q192R polymorphism on serum FABP4 levels in Mexican women.

Methods: PON1 Q192R polymorphism was genotyped using a TaqMan allelic discrimination assay and serum FABP4 concentration was measured using an enzyme-linked immunosorbent assay.

Results: The distribution of genotype frequencies in the assessed women (PON1 Q192R polymorphism) was QQ?=?20%, QR?=?48% and RR?=?32%. Significantly higher serum FABP4 levels were found in women with genotype QR/RR (20.6?±?2.20?ng/mL), when compared with the levels found in the QQ group (12.8?±?1.70?ng/mL) (p?=?.004). After, the odds ratio (OR) was calculated by binomial logistic regression analysis and a significantly higher OR was found in the QR/RR group when compared with the QQ group (OR?=?3.45; 95% CI?=?1.80–16.50; p?Conclusion: The results support an association between 192R-allele of the PON1 polymorphism (Q192R) and increased serum FABP4 levels (suggested as an early biomarker of CVDs risk) in assessed Mexican women.     

A Single Nucleotide Polymorphism of IL-21 Gene is Associated with Systemic Lupus Erythematosus in a Chinese Population

The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in IL-21 gene with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A total of 605 independent SLE patients and 666 unrelated healthy controls were recruited for the case?Ccontrol association study. Two SNPs (rs2221903 and rs907715) within the IL-21 gene intronic region were genotyped by TaqMan SNP allelic discrimination methods. The allele T frequency of SNP rs2221903 in patients and healthy controls was 89.4?% and 86.8?%, respectively [T versus C, odds ratio (OR)?=?1.287, 95?% confidence interval (CI)?=?1.010?C1.640]. No significant differences in genotype frequencies were shown between SLE patients and healthy controls (P value?=?0.705, 0.406, respectively). However, the effect of recessive model (TT versus CC?+?CT, OR?=?1.368, 95?% CI?=?1.050?C1.781) was observed. Distributions of allele and genotype frequencies of the SNP rs907715 showed no significant differences between SLE patients and controls. Analysis of the haplotypes revealed that CC haplotype was significantly associated with SLE (OR?=?0.734, 95?% CI?=?0.573?C0.941). In conclusion, our findings suggest that a SNP (rs2221903) and CC haplotype (rs2221903 and rs907715) of the IL-21 gene is associated with SLE in the Chinese population. However, further studies are needed to determine the functional consequences of this polymorphism with SLE susceptibility.     

Association between ADAM33 T1 polymorphism and susceptibility to asthma in Asians

Objective

The aim of this study was to determine whether the ADAM33 (a disintegrin and metalloproteinase domain 33) T1 (rs2280091), T2 (rs2280090), and ST+7 (rs574174) polymorphisms confer susceptibility to asthma.

Methods

A meta-analysis stratified by ethnicity and age was conducted on associations between the ADAM33 T1, T2, and ST+7 polymorphisms and asthma.

Results

Eleven studies, which included 4,124 patients and 7,094 controls, were available for the meta-analysis. Meta-analysis revealed an association between asthma and the ADAM33 T1 GG genotype [odds ratio (OR)?=?2.257, 95?% confidence interval (CI)?=?1.577–3.228, p?=?8.42?×?10^?7]. Stratification by ethnicity indicated an association between this genotype and asthma in Asians (OR?=?2.683, 95?% CI?=?1.799–4.001, p?=?1.31?×?10^?7), and stratification by age indicated an association between it and asthma in adults (OR?=?1.895, 95?% CI?=?1.005–3.573, p?=?0.048). However, no association was found between asthma and the ADAM33 T2 and ST+7 polymorphisms.

Conclusions

This meta-analysis demonstrates that the ADAM33 T1 polymorphism confers susceptibility to asthma in Asians, but no association was found between the ADAM33 T2 and ST+7 polymorphisms and asthma susceptibility.     

Association of E-selectin Gene Polymorphism (S128R) with Ischemic Stroke and Stroke Subtypes

E-selectin is an important inflammatory cytokine involved in the pathogenesis of various diseases such as atherosclerosis and stroke. We investigated the association of E-selectin gene polymorphism (S128R) with ischemic stroke and its subtypes. We studied 610 patients with ischemic stroke and 610 age- and sex-matched healthy controls. The ischemic stroke was classified according to Trial of Org10172 in Acute Stroke Treatment (TOAST). E-selectin gene polymorphism (S128R) was determined by polymerase chain reaction–restriction fragment length polymorphism technique. We found statistically significant difference in the genotypic distribution between patients and controls (for AC vs. AA, χ ²?=?49.5; p?<?0.001, odds ratio?=?5.47(95 % CI, 3.25–9.21). A significant difference was observed in the frequency of C and A alleles in patients and controls (for C vs. A, χ ²?=?47.4; p?<?0.001, odds ratio?=?5.13 (95 % CI, 3.06–8.57). Multiple logistic regression analysis revealed that the most predictive risk factor for stroke was AC genotype (adjusted odds ratio?=?1.450 (95 % CI, 1.23–2.75) and p?=?0.001), hypertension, smoking, and diabetes (p?=?0.001 in each case). We also found a significant association of AC genotype with intracranial large artery atherosclerosis (p?<?0.01, odds ratio?=?9.37, (95 % CI, 5.31–16.5) and small artery occlusion (p?<?0.0001, odds ratio?=?9.81 (95 % CI, 4.94–19.4). Our results indicate that the individuals bearing AC genotype of E-selectin gene polymorphism (S128R) are more prone to stroke than AA genotype.     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

The relevance of Tim-3 polymorphisms and F protein to the outcomes of HCV infection

Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR)?=?0.54, 95 % confidence interval (CI)?=?0.35–0.83, p?=?0.005; OR?=?0.26, 95 % CI?=?0.18–0.39, p?<?0.001; and OR?=?0.19, 95 % CI?=?0.10–0.35, p?<?0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR?=?1.70, 95 % CI?=?1.20–2.40, p?=?0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR?=?0.22, 95 % CI?=?0.14–0.33, p _trend?<?0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT?+?TT) genotypes were significantly lower in the older (OR?=?0.31, 95 % CI?=?0.15–0.65, p?=?0.002) and female (OR?=?0.30, 95 % CI?=?0.17–0.52, p?<?0.001) subgroups, and rs13170556 (TC?+?CC) genotypes exhibited the same effect in all subgroups (all p?<?0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC?+?CC) genotypes were significantly more frequent in the younger (OR?=?1.86, 95 % CI?=?1.18–2.94, p?=?0.007) and female (OR?=?2.38, 95 % CI?=?1.48–3.83, p?<?0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.     

The association between endothelial nitric oxide synthase gene G894T polymorphism and hypertension in Han Chinese: a case-control study and an updated meta-analysis

Background: The G894T (rs1799983) polymorphism in endothelial nitric oxide synthase (eNOS/NOS3) gene has been implicated in susceptibility to essential hypertension (EH) in some studies, but no clear consensus has been reached in the Chinese population.

Aims: This study aimed to investigate the association of the G894T polymorphism and EH in Han Chinese.

Subjects and methods: First, a case-control study was performed involving 1525 subjects in northern Han Chinese to study the association between G894T variants and EH and then a meta-analysis was conducted of all available studies in Han Chinese. A total of 25 studies comprising 13?443 subjects were finally included in this meta-analysis.

Results: The present case-control study failed to show significant association of G894T variant with EH in northern Han Chinese. The subsequent meta-analysis showed that this polymorphism might be associated with EH in Han Chinese (p?p?p?=?0.12, OR?=?1.16). The meta-regression analysis suggested that the geographic difference of subjects was related to heterogeneity (p?=?0.029).

Conclusions: The relationship between the G894T polymorphism and hypertension in Han Chinese may be attributed to the difference in geographic background of subjects. It is necessary to carry out further research with a large sample size and focusing on gene–environment interactions.     

Associations between interleukin-23R and interleukin-12B polymorphisms and psoriasis susceptibility: a meta-analysis

Objective: The aim of this study was to determine whether interleukin (IL)-23?R and IL-12B polymorphisms confer susceptibility to psoriasis.

Methods: The authors conducted a meta-analysis on associations between the IL-23?R and IL-12B polymorphisms and psoriasis susceptibility.

Results: A total of 14 comparison studies were included in this meta-analysis. The meta-analysis identified a significant association between psoriasis and 2 alleles of the rs11209026 and rs7530511 polymorphisms in Europeans (odds ratio [OR]?=?0.624, 95% confidence interval [CI]?=?0.565–0.697, p?<?1.0?×?10^?8; OR?=?0.804, 95% CI?=?0.743–0.869, p?=?3.0?×?10^?7, respectively). Meta-analysis of IL-12B showed a significant association between the 2 alleles of the rs6887695 and rs3212227 polymorphisms and the risk of developing psoriasis (OR?=?0.710, 95% CI?=?0.673–0.749, p?<?1.0?×?10^?8; OR?=?0.684, 95% CI?=?0.639–0.731, p?<?1.0?×?10^?8, respectively). Stratification by ethnicity identified an association between the rs6887695 and rs3212227 polymorphisms and psoriasis in Europeans.

Conclusions: This meta-analysis showed that the IL-23?R (rs11209026 and rs7530511) polymorphisms are associated with psoriasis risk in Europeans and that the IL-12B (rs6887695 and rs3212227) polymorphisms are associated with susceptibility to psoriasis in Europeans.     

Physical inactivity and cognitive impairment in Korean older adults: gender differences in potential covariates

Background: Physical inactivity is one major lifestyle risk factor of mild cognitive impairment with ageing.

Aim: To investigate whether or not potential covariates modulate the association between physical activity (PA) and cognitive impairment in older adults.

Subjects and methods: Data from 10?245 Korean older adults (5817 women) were used.

Results: High PA older adults were younger and longer educated and had lower comorbidity and depression than low PA older adults. Compared with low PA men, moderate PA men only had a significantly lower odds-ratio (OR) and 95% confidence interval (95% CI) (OR?=?0.795, 95% CI?=?0.654?～?0.965, p?=?0.021) for having cognitive impairment, even after adjusting for measured covariates, which was no longer significant when additionally adjusted for comorbidity (OR?=?0.862, 95% CI?=?0.707?～?1.051, p?=?0.143). Compared with low PA women, moderate and high PA women had significantly lower risks of cognitive impairment (OR?=?0.830, 95% CI?=?0.712?～?0.969, p?=?0.018 and OR?=?0.784, 95% CI?=?0.651?～?0.943, p?=?0.010, respectively), even after adjusting for the measured covariates including comorbidity, which was no longer significant when additionally adjusted for depression (OR?=?0.897, 95% CI?=?0.776?～?1.049, p?=?0.173 and OR?=?0.919, 95% CI?=?0.761?～?1.111, p?=?0.385, respectively).

Conclusion: These findings suggest that gender differences in the covariates modulate the relationship between physical activity and cognitive decline in older Korean adults.     

The variations in the IL1RL1 gene and susceptibility to preeclampsia

The IL1RL1, which encodes at least three isoforms by alternative splicing, has been identified to be involved in the initiation and perpetuation of inflammation. In spite of being a main contributor of maternal and perinatal mortality, the mechanism responsible for the pathophysiology of preeclampsia has not yet been well addressed. To investigate the relationship between IL1RL1 polymorphisms and preeclampsia risk, we identified the correlation between three tag SNPs (rs13017455, rs1420103 and rs17027006) in IL1RL1 with preeclampsia risk in a case-control study. A total of 214 cases and 208 controls were recruited to participate in this study. Genotypes of the three SNPs were determined with the use of polymerase chain reaction-restriction fragment length polymorphism assay. Significantly reduced preeclampsia risk was found to be associated with the CT genotype of rs13017455 (p?=?0. 032, OR?=?0. 66, 95% CI?=?0.45–0.97) in overdominant model. Differences were particularly significant in the severe preeclampsia subgroup (p?=?0.045, OR?=?0.66, 95% CI?=?0.44–0.99) and the early-onset severe preeclampsia subgroup (p?=?0.0097, OR?=?0.47, 95% CI?=?0.26–0.84). Significantly increased mild preeclampsia risk was observed associated with GG genotype of rs1420103 polymorphisms (p?=?0.029, OR?=?2.18, 95% CI?=?1.09–4.34), while reducing late-onset severe preeclampsia susceptibility was associated with TT genotype of rs1420103 (p?=?0.02, OR?=?0.49, 95% CI?=?0.26–0.92).