Lack of association between Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms and tuberculosis susceptibility: A meta-analysis

ObjectiveToll-like receptor 4 (TLR4) plays a vital role in immunity to tubercle bacillus and its gene polymorphisms are supposed to affect tuberculosis susceptibility in some rather than all studies. Then, we integrated published data and performed a comprehensive meta-analysis to get more reliable estimations for the strength of associations between TLR4 gene polymorphisms and the risk of tuberculosis.MethodsWe systematically searched the electronic PubMed database for research articles about TLR4 gene polymorphisms and tuberculosis up to February 2012. Revman 5.0 software was adopted to conduct the meta-analysis. Crude odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated by either fixed-effects model or random-effects model.ResultsFinally, six case-control studies were identified, involving 1587 controls and 2110 patients. Overall, no significant associations were found between TLR4 gene Asp299Gly polymorphism and tuberculosis in the codominant models (GG vs AA: OR = 1.56, 95% CI = 0.76–3.21, P = 0.23; GA vs AA: OR = 1.01, 95% CI = 0.84–1.23, P = 0.89), the dominant model (GG + GA vs AA: OR = 1.04, 95% CI = 0.80–1.35, P = 0.75), the recessive model (GG vs GA + AA: OR = 1.55, 95% CI = 0.75–3.19, P = 0.24) and the allele model (G vs A: OR = 1.06, 95% CI = 0.81–1.40, P = 0.66). Similarly, no significant associations between TLR4 gene Thr399Ile and tuberculosis were observed (all P > 0.05).ConclusionsThe present meta-analysis suggests that TLR4 gene Asp299Gly and Thr399Ile polymorphisms are not associated with the susceptibility of tuberculosis.     

The NRAMP1, VDR,TNF-α, ICAM1, TLR2 and TLR4 gene polymorphisms in Iranian patients with pulmonary tuberculosis: A case–control study

The innate immune response drives early events in Mycobacterium tuberculosis infection. Since human genetic variation is an important determinant in the outcome of infection with M. tuberculosis, we typed polymorphisms in the innate immune molecules, such as natural-resistance-associated macrophage protein 1 (NRAMP1), Vitamin D receptor (VDR), Tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule1 (ICAM-1), Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in a case–control study of pulmonary tuberculosis in Iranian population.We conducted an association study and included 96 patients and 122 matched healthy individuals. We used single ARMS-PCR technique to simultaneously genotype fourteen polymorphisms in this survey.Among all fourteen polymorphisms that were examined, three polymorphisms were significantly different between case and control groups. The TNF − 308A polymorphism showed significant increase in allele and genotype frequencies among patients compared to control individuals [− 308A allele: 19.3 vs. 9.4%, GA genotype: 28.1 vs. 17.2%, AA genotype: 5.2 vs. 0.8%; Corrected P (Pc) < 0.05], and the TLR4 variant allele and genotypes prevalence (D299G and T399I) were significantly higher among patients compared to controls [DG genotype: 14.6 vs. 5.7%, Pc < 0.05 and I399 allele: 4.2 vs. 0.8%, TI genotype: 8.3 vs. 1.6%; Pc < 0.05], respectively.In conclusion, our data suggest that TLR4 (D299G and T399I) and TNF (− 308G/A) genetic polymorphisms may influence the risk of developing tuberculosis after exposure to Mycobacterium.     

Toll-like receptor 7 variations are associated with the susceptibility to HCV infection among Chinese females

Toll-like receptors 7 (TLR7) play a crucial role in provoking an immune response in HCV infection. We aimed to investigate whether single nucleotide polymorphisms (SNPs) of TLR7, including rs179009, rs179010 and rs179012, affect the outcomes of HCV infection among the Chinese population. A total of 1767 Chinese Han individuals were enrolled. The distribution of SNP frequencies among three groups with different outcomes of HCV infection was assessed, including healthy controls, cases with spontaneous clearance and cases with viral persistence. Then TLR7 mRNA expression and the production of IFN-α and IL-6 after TLR7 agonist Imiquimod stimulation in vitro were determined. Our results suggested that rs179009 GG genotype was significantly associated with a higher risk of the susceptibility to HCV infection among female subjects (OR = 2.42, 95% CI = 1.24–4.71, P = 0.01). Haplotype GCG was significantly associated with a high risk for HCV susceptibility (OR = 1.50, 95% CI = 1.11–2.03, P = 0.01) as compared with the reference haplotype ACG among females. In the functional research of rs179009, a lower IFN-α level was observed in GG genotype than in AA genotype (P = 0.032). Our data indicate that TLR7 rs179009 GG genotype and haplotype GCG were associated with an increased risk of the susceptibility to HCV infection among Chinese females, which may be due to the impaired IFN-α response.     

Influence of common variants of TLR4 and TLR9 on clinical outcomes of Plasmodium falciparum malaria in Odisha,India

BackgroundIn malaria, the toll-like receptors (TLRs) have recently emerged as major player of innate immunity. However, implication of TLR variants on clinical manifestations of malaria is conflicting. The present study aims to provide relevant information of growing interest in understanding the role of TLR4D299G, TLR9T-1237C and TLR9T-1486C polymorphisms on clinical outcomes of malaria.MethodsWe genotyped TLR4D299G, TLR9T-1237C and TLR9T-1486C polymorphisms by PCR-RFLP methods and subsequently analyzed in 200 uncomplicated patients and 200 severe patients. Further, the severe malaria categorized into sub-clinical groups such as cerebral malaria (CM), non-cerebral severe malaria (NCSM), single organ dysfunction (SOD) and multi-organ dysfunctions (MODS) are analyzed.ResultThe TLR9-1237CC genotype was observed at significantly low frequency in MODS (p = 0.0008), while in heterozygous state (TC) it was proportionately more frequent in SOD (p = 0.087) as compared to mild malaria. The TLR9T-1486C heterozygote was more common in all categories of severe malaria. However, pair wise LD analysis revealed significant linkage between T-1237C and T-1486C, whereas haplotype analysis showed significantly low frequency of C-T haplotype in CM (p = 0.005, p_c = 0.02) and high frequency of T-C haplotype in NCSM as compared to mild malaria.ConclusionAlthough TLR9-1237C could be a risk factor for severe malaria in heterozygous state, negative association of CC genotype with MODS warrants caution of segregating severe malaria into its sub-clinical groups while interpreting data. Further, clinical outcome in malaria was observed to be apparently modulated by LD between TLR9 promoter variants.     

NRAMP1 D543N and INT4 polymorphisms in susceptibility to pulmonary tuberculosis: A meta-analysis

The association of natural resistance associated macrophage protein 1 (NRAMP1) polymorphisms (D543N, INT4) with pulmonary tuberculosis (PTB) risk have been widely reported. However, the findings of previous studies were inconsistent. To clarify the role of these polymorphisms in PTB, we performed a meta-analysis of all available and relevant published studies. Based on comprehensive searches of the PubMed, Medline, Embase, Web of Science, Elsevier Science Direct and Cochrane Library database, we identified outcome data from all articles estimating the association between NRAMP1 polymorphisms and PTB risk. For D543NA/G polymorphism, no associations were found in all genetic models. For INT4C/G polymorphism, significant increased PTB risk was observed in recessive model (CC vs. GC + GG: P = 0.025, OR = 1.35, 95% CI = 1.04–1.75). In the subgroup analysis by ethnicity, significantly increased risk were observed for D543NA/G polymorphism in Americans (GA vs. GG: P = 0.03, OR = 1.31, 95% CI = 1.03–1.67; AA + AG vs. GG: P = 0.032, OR = 1.29, 95% CI = 1.02–1.63). Moreover, the INT4C/G polymorphism was also associated with increased risk of TB for Africans in allele model (A vs. G: P = 0.012, OR = 1.41, 95% CI = 1.08–1.85), heterozygous model (GA vs. GG: P = 0.004, OR = 1.53, 95% CI = 1.14–2.04) and dominant model (AA + AG vs. GG: P = 0.007, OR = 1.49, 95% CI = 1.12–1.98). This meta-analysis provides evidences that INT4C/G was associated with increased susceptibility to pulmonary tuberculosis in overall population in recessive model. D543NA/G polymorphism was associated with PTB increased risk in Americans, while INT4C/G polymorphism in Africans. Further well-designed, large scale studies are required to confirm this conclusion.     

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 between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users

BackgroundTLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection.Materials and methodsA total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay.ResultsThe TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors – 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p = 0.037 and 80% vs. 53%; p = 0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR = 0.29, 95% CI = 0.09–0.90). This association remained significant (OR = 0.25, 95% CI = 0.07–0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use).ConclusionsThe TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.     

Dengue vaccine acceptance and associated factors in Indonesia: A community-based cross-sectional survey in Aceh

BackgroundThe first dengue vaccine (DV) has been licensed in some countries, but an assessment of the public's acceptance of DV is widely lacking. This study aimed to explore and understand DV acceptance and its associated explanatory variables among healthy inhabitants of Aceh, Indonesia.MethodsA community-based cross-sectional survey was conducted from November 2014 to March 2015 in nine regencies of Aceh that were selected randomly. A set of validated questionnaires covering a range of explanatory variables and DV acceptance was used to conduct the interviews. A multi-step logistic regression analysis and Spearman's rank correlation were employed to assess the role of explanatory variables in DV acceptance.ResultsWe included 652 community members in the final analysis and found that 77.3% of them were willing to accept the DV. Gender, monthly income, socioeconomic status (SES), attitude toward dengue fever (DF) and attitude toward vaccination practice were associated with DV acceptance in bivariate analyses (P < 0.05). A correlation analysis confirmed that attitude toward vaccination practice and attitude toward DF were strongly correlated with DV acceptance, r_s = 0.41 and r_s = 0.39, respectively (P < 0.001). The multivariate analysis revealed that a high monthly income, high SES, and a good attitude toward vaccination practice and toward DF were independent predictors of DV acceptance.ConclusionThe acceptance rate of the DV among inhabitants of Aceh, Indonesia was relatively high, and the strongest associated factors of higher support for the DV were a good attitude toward vaccination practices and a good attitude toward DF.     

Association of human leukocyte antigen DP/DQ gene polymorphisms with chronic hepatitis B in Chinese Han and Uygur populations

Several genome-wide association studies (GWAS) have shown that human leukocyte antigen (HLA) DP/DQ gene polymorphisms are associated with susceptibility to chronic hepatitis B virus (HBV) infection. We clarified the roles of the HLA-DP/DQ gene in HBV infection in different nationalities. Three single nucleotide polymorphisms (SNPs) in HLA-DP (rs9277471, rs9277535 and rs9277542) and the SNP rs9272346 in HLA-DQ were studied. In total, 779 patients were recruited to this study, including 400 Chinese Han and 399 Uygurs. The rs9277535 variant genotypes were directly associated with HBV persistence compared to healthy controls in an additive model of the Chinese Han population (odds ratio [OR] = 1.88, 95% confidence interval [CI] = 1.03–3.41, P = 0.040), and in a recessive model of the Chinese female population (OR = 2.02, 95% CI = 1.26–3.24, P = 0.003). In addition, rs9277471 and rs9277542 variant genotypes significantly decreased the risk of HBV infection compared to healthy controls in an additive model of the Chinese Han population (OR = 0.53, 95% CI = 0.29–0.98, P = 0.042; OR = 0.53, 95% CI = 0.29–0.97, P = 0.039) and in a dominant model of the Chinese female population (OR = 0.50, 95% CI = 0.31–0.80, P = 0.004; OR = 0.49, 95% CI = 0.31–0.79, P = 0.003). The GG genotype of rs9277346 was associated with HBV infection in the Chinese Han population (additive model: OR = 0.38, 95%CI = 017–0.82, P = 0.014; recessive model: OR = 0.41, 95% CI = 0.19–0.86, P = 0.019) and in males (additive model: OR = 0.31, 95% CI = 0.14–0.65, P = 0.002; dominant model: OR = 0.65, 95% CI = 0.43–0.97, P = 0.034; recessive model: OR = 0.36, 95% CI = 0.18–0.73, P = 0.005). In addition, allele G of rs9277346 was marginally related to a reduction in risk for HBV infection in the Uygur population. Our study suggests that HLA-DP/DQ polymorphisms can affect susceptibility and resistance to HBV infection in Chinese populations, and are possibly linked to race and sex.     

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.     

A meta-analysis of psycho-behavioral obesity interventions among US multiethnic and minority adults

ObjectiveThe present review examines efficacious psycho-behavioral interventions in preventing weight gains or reducing weight among US multiethnic and minority adults as few studies were conducted to review such interventions to date.MethodsData were examined from 24 controlled intervention studies, representing 23 programs and involving 13,326 adults. Studies were identified through manual and online search of databases that include MEDLINE, Academic Search Premier, ERIC, PsycARTICLES, SPORTDiscus, and CINAHL Plus.ResultsWhereas one-component (n = 5, d = 0.08, 90% CI = − 0.04, 0.35) and two-component interventions (n = 13, d = 0.22, 90% CI = 0.05, 0.40) showed a low mean effect size, three-component interventions (n = 6, d = 0.52, 90% CI = 0.39, 0.65) showed a moderate effect size. Interventions conducted in individual sessions (n = 15, d = 0.40, 90% CI = 0.24, 0.56) showed a higher mean effect size than group interventions (n = 9, d = 0.08, 90% CI = − 0.04, 0.30) although the confidence intervals overlapped.ConclusionsThe study results indicate that future obesity prevention interventions targeting multiethnic and minority adults might benefit from incorporating individual sessions, family involvement, and problem solving strategies into multi-component programs that focus on lifestyle changes.     

Toll-like receptor 8 (TLR8) polymorphisms are associated with non-progression of chronic hepatitis C in HIV/HCV coinfected patients

Toll-like receptor 8 (TLR8) polymorphisms have been related to hepatitis C virus (HCV) infection. The aim was to estimate the association of TLR8 polymorphisms with HCV-related outcomes in HIV/HCV coinfected patients. We performed a cross-sectional study of 220 patients who underwent a liver biopsy. TLR8 polymorphisms were genotyped using GoldenGate® assay. The outcome variables were non-fibrosis (F0), mild-inflammation (A0/A1), and non-steatosis [fatty hepatocytes (FH) < 10%]. Logistic regression analysis was used to compare the outcome variables according to TLR8 polymorphisms. Four polymorphisms were analyzed (rs1013151, rs5744069, rs17256081 and rs3764880rs1013151). Female patients had higher frequency of TLR8 major alleles at rs17256081 and rs101315, and minor alleles at rs3764880 and rs5744069. Male patients had higher frequency of TLR8 minor alleles except for rs3764880, where major alleles were higher (p < 0.01). Two TLR8 polymorphisms (rs1013151 and rs5744069) were significantly associated with non-fibrosis (F0) [adjusted odds ratio (aOR) = 4.42 (95% of confidence interval (95%CI) = 1.54; 12.68) (p = 0.006) and aOR = 4.76 (95%CI = 1.69; 13.37) (p = 0.003); respectively]. When data were stratified by gender, rs1013151 and rs5744069 polymorphisms remained significant for male patients [adjusted odds ratio (aOR) = 4.49 (95%CI = 1.08; 18.62) (p = 0.039) and aOR = 6.17 (95%CI = 1.45; 26.20) (p = 0.014); respectively]. When data were stratified by major HCV genotypes, patients infected with HCV genotype 1 (GT1) had significant values for both rs1013151 and rs5744069 polymorphisms [aOR = 5.79 (95%CI = 1.44; 23.32) (p = 0.013) and aOR = 8.01 (95%CI = 2.16; 35.65) (p = 0.005); respectively]. Finally, none of the TLR8 polymorphisms were significantly associated with mild-inflammation or non-steatosis. In conclusion, TLR8 polymorphisms seem to be related to non-progression of liver fibrosis in HIV/HCV coinfected patients, particularly in males and those patients infected with GT1.     

Genetic variation in IL28RA is associated with the outcomes of HCV infection in a high-risk Chinese population

Hepatitis C virus (HCV) infection varies in the outcomes depending on both viral and host factors. This study aims to investigate the association of single-nucleotide polymorphisms (SNPs) of IFNAR2, IL10RB, and IL28RA genes with susceptibility to HCV infection and resolution. Genotyping of IFNAR2, IL10RB, and IL28RA gene polymorphisms were performed using TaqMan® method from 552 patients with sero-positive anti-HCV and 421 uninfected controls. The distribution of IFNAR2 and IL10RB genotypes among the control, persistent infection, and spontaneous clearance groups did not differ. However, IL28RA-rs10903035 A allele was over-represented in persistent infection group when compared with uninfected controls and spontaneous clearance group, respectively (OR = 1.54, 95%CI = 1.23–1.92, P = 0.004; OR = 1.42, 95%CI = 1.12–1.81, P = 0.016), and AA genotype had a significant increased risk of persistent infection in different strata except for the females subgroup (P < 0.05). IL28RA-rs11249006 GG genotype showed reduced susceptibility to persistent HCV infection (OR = 0.53, 95%CI = 0.31–0.91, P = 0.044), and the protective effect was significantly different among subgroups stratified by age and likely source of infection (P < 0.05). Besides, AG genotype had a significant negative effect on spontaneous clearance of HCV among young subjects (aged ?40) and patients infected with viral genotype-1 (P < 0.05). Stratified analysis also showed that IL10RB-rs2834167 AG genotype was associated with an increased risk of persistent HCV infection in females, and GG genotype was associated with an increased risk of persistent HCV infection in females and patients with viral genotype non-1 (P < 0.05). Haplotype analysis showed that IL28RA rs10903035-rs11249006 haplotype GG played a protective effect for HCV infection (OR = 0.21, 95%CI = 0.13–0.36, P < 0.001; OR = 0.20, 95%CI = 0.12–0.34, P < 0.001). This study indicates that two SNPs in IL28RA are correlated with susceptibility to HCV infection and spontaneous viral clearance, which implicates a primary role of IL28RA in the outcomes of HCV infection.     

Melanocortin-3 receptor gene variants: Association with childhood obesity and eating behavior in Chilean families

ObjectiveTo evaluate the association between melanocortin-3 receptor common genetic polymorphisms with childhood obesity and eating behavior in Chilean families.MethodsTwo hundred twenty-nine obese children (6–12 y old, body mass index >95th percentile of Centers for Disease Control and Prevention/National Center for Health Statistics, 2000) and 270 parents were selected. Genotypes for MC3R genetic markers ?239A > G, 17C > A (Thr6Lys), 241 G > A (Val81Ile), +2138InsCAGACC, and microsatellite D20s32e were determined. Eating behavior scores were computed using the Child Eating Behavior Questionnaire and a shorter version of the Three Factor Eating Questionnaire adapted for evaluating eating inclinations in children. Genotype-obesity associations were assessed by the Transmission Disequilibrium Test. Non-parametric tests were used to compare eating behavior scores across study groups.ResultsAllelic frequencies of ?239 G, 17A, 241A, and +2138InsCAGACC were estimated as 4.5%, 5.9%, 5.6%, and 17.6%, respectively, in obese children. The Transmission Disequilibrium Test in case–parent trios revealed no significant associations between childhood obesity and genetic markers, including the microsatellite D20s32e. In girls, we found significantly higher scores of the emotional eating subscale in carriers of the +2138InsCAGACC compared with non-carriers (P = 0.04). In boys, carriers of 17A and 241A showed lower scores for the emotional eating subscale (P = 0.01), whereas carriers of +2138InsCAGACC showed significantly lower scores for the enjoyment of food subscale compared with non-carriers (P = 0.04).ConclusionsThere is not sufficient evidence to support the contribution for common melanocortin-3 receptor variants in childhood obesity. However, our results are concordant for a role of melanocortin-3 receptor variants in some dimensions of eating behavior such as emotional eating and enjoyment of food.     

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.     

Évolution du statut nutritionnel d’une cohorte d’enfants tunisiens au cours de l’hospitalisation : facteurs de risque de la dénutrition hospitalière

ObjectivesStudy the evolution of the nutritional status of a cohort of hospitalized children and identify the risk factors of hospital malnutrition.MethodsProspective, cross-sectional study carried out in a pediatric department over a period of six months, including all children aged ≥ 30 days, hospitalized for a period ≥ six days. Anthropometric data were assessed on admission and discharge. Food consumption was assessed using the flower tool. We identified the risk factors for hospital undernutrition (HUN) by multivariate analysis.ResultsWe included 120 patients with a mean age 46.3 months. The prevalence of acute undernutrition at admission was 21.7% and that of chronic undernutrition was 10%. The prevalence of acute undernutrition at discharge rose to 34%. Weight loss during hospitalization was noted in 68.3% of cases. The prevalence of HUN was 55% considering a decrease in BMI or P/PAT z-score ≥ 25%. The risk factors for HUN were: age ≤ 24 months (P = 0.039; OR 95% CI = 2.67 [1.05–6.82]), the presence of undernutrition on admission (P = 0.002; OR 95% CI = 2.32 [0.93–6.51]) and average food consumption < 50% during hospitalization (P < 10^?3; OR 95% CI = 6.69 [2.57–17.40]).ConclusionScreening for undernutrition on admission to hospital as well as assessment of the nutritional risk in hospitalized children is essential so that preventive or curative nutritional care can be taken.     

Eficacia de un programa de automedida domiciliaria de la presión arterial como estrategia para disminuir la inercia terapéutica

ObjectiveTo evaluate the efficacy of a program of home blood pressure monitoring (HBPM) on therapeutic Inertia (TI) in mild-to-moderate hypertension (AHT).DesignControlled, randomised clinical trial.SettingForty six clinics in 35 primary care centres. Spain.ParticipantsA total of 232 patients with uncontrolled hypertension were included.InterventionTwo groups with 116 patients were formed: 1) Control group (CG): standard health intervention; 2) Intervention group (IG): patients who were included in the HBPM program.Main measurementsTI was calculated by the ratio: Number of patients whose pharmacological treatment was not changed in each visit/Number of patients with an average BP 140mmHg and/or 90mmHg in the general population or 130 and/or 90 mmHg in diabetics. The mean BPs and the percentage of controlled patients were calculated. The mean number of people that required an intervention in order to avoid TI was calculated (NI).ResultsA total of 209 patients completed the study, with TI in 35.64% (95% CI = 29.85%-41.43%) of the sample, and in 71.63% (95% CI = 63.9-79.36%) of the uncontrolled hypertensive patients.The TI was 22.42% (95% CI = 24.2-37%) in the IG and 50% (95% CI = 37.75-62.25) in the CG (p < .05) in visit 2, and 25.23% (95% CI = 14.84-35.62) and 46.07% (95% CI = 33.85-58.29) in the final visit for IG and CG, respectively (P < .05). The NI was 4.3.ConclusionsTI was very significant among the uncontrolled hypertensive patients. The studied interventions are effective for improving TI.     

Exonic single nucleotide polymorphisms within TLR3 associated with infant responses to serogroup C meningococcal conjugate vaccine

The introduction of the serogroup C meningococcal (MenC) conjugate vaccination has successfully controlled the burden of disease associated with this serogroup in many countries. However, considerable inter-individual variation is observed in immune responses to MenC vaccine, and little is understood of the determinants of this variability. Previously, we reported an association between single nucleotide polymorphisms (SNPs) in TLR3 and CD44 and the persistence of MenC vaccine immunity. Here we further examine polymorphisms within these two candidate genes and immune responses to MenC vaccine. MenC-specific IgG concentrations and serum bactericidal assay (SBA) titres were measured one month after a primary course of MenC vaccination in 318 human infants. Tagging SNPs (TagSNPs) within TLR3 and CD44 were genotyped and regional imputations carried out to screen these genes for variations associated with immunological responses to MenC vaccine. This study reports an association between an exonic variant (rs3775290, P = 0.025) in TLR3 and MenC IgG concentrations, as well as an association between three SNPs in CD44 (rs3794109, P = 0.021; rs3794110, P = 0.022; rs112762, P = 0.049) and MenC SBA titres. These data support our previous findings of an association between SNPs in TLR3 and CD44, and present novel findings implicating exonic variants in these genes with MenC vaccine responses.