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.     

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.     

Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women

Small, noncoding RNA molecules, called microRNAs (miRNAs), are thought to function as either tumor suppressors or oncogenes. Common single-nucleotide polymorphisms (SNPs) in miRNAs may change their property through altering miRNA expression and/or maturation, and thus they may have an effect on thousands of target mRNAs, resulting in diverse functional consequences. However, it remains largely unknown whether miRNA SNPs may alter cancer susceptibility. We evaluated the associations of selected four SNPs (rs2910164, rs2292832, rs11614913, and rs3746444) in pre-miRNAs (hsa-mir-146a, hsa-mir-149, hsa-mir-196a2, and hsa-mir-499) with breast cancer risk in a case-control study of 1,009 breast cancer cases and 1,093 cancer-free controls in a population of Chinese women and we found that hsa-mir-196a2 rs11614913:T>C and hsa-mir-499 rs3746444:A>G variant genotypes were associated with significantly increased risks of breast cancer (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.02-1.48 for rs11614913:T>C; and OR, 1.25; 95% CI, 1.02-1.51 for rs3746444:A>G in a dominant genetic model) in a dose-effect manner (P for trend was 0.010 and 0.037, respectively). These findings suggest, for the first time, that common SNPs in miRNAs may contribute to breast cancer susceptibility. Further functional characterization of miRNA SNPs and their influences on target mRNAs may provide underlying mechanisms for the observed associations and disease etiology.     

The association between interleukin-6 polymorphisms and rheumatoid arthritis: a meta-analysis

Objective

The aim of this study was to determine whether the functional interleukin-6 (IL-6) promoter ?174 G/C and ?572 G/C polymorphisms confer susceptibility to rheumatoid arthritis (RA) in ethnically different populations.

Methods

Meta-analysis was conducted on the associations between these IL-6 polymorphisms and RA.

Results

A total of nine studies involving 3,851 subjects (RA 2,053 and controls 1,798) were considered in this study and ethnicity-specific meta-analysis was performed on European subjects. In all study subjects, meta-analysis revealed a trend toward to an association between RA and the IL-6 ?174 G allele (odds ratio [OR]?=?0.699, 95?% confidence interval [CI]?=?0.463–1.054, p?=?0.088). Stratification by ethnicity indicated a significant association between RA and the IL-6 ?174 G/C polymorphism in Europeans using the dominant (OR?=?0.329, 95?% CI?=?0.155–0.699, p?=?0.004) and recessive (OR?=?0.823, 95?% CI?=?0.679–0.997, p?=?0.047) models. Meta-analysis of the IL-6 ?572 G/C polymorphism showed no association between RA and the IL-6 ?572 G allele in all study subjects (OR?=?1.641, 95?% CI?=?0.613–4.397, p?=?0.324).

Conclusions

This meta-analysis shows that the IL-6 ?174 G/C polymorphism may confer susceptibility to RA in Europeans.     

Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis

Objective

The aim of this study was to determine whether phox homology domain containing serine/threonine kinase (PXK) and tyrosine kinase 2 (TYK2) confer susceptibility to systemic lupus erythematosus (SLE).

Materials and methods

The authors conducted meta-analyses on associations between SLE susceptibility and the rs6445975 polymorphism of PXK and the rs2304256, rs12720270, rs280519, and rs1272036 polymorphisms of TYK2.

Results

A total of 13 separate comparisons studies were included in this meta-analysis. Meta-analysis identified an association between SLE and the 2 allele of the rs6445975 polymorphism in the overall population [odds ratio (OR)?=?1.151, 95?% confidence interval (CI)?=?1.086–1.291, P?=?1.8E?06]. Stratification by ethnicity identified a significant association between this polymorphism and SLE in Europeans (OR?=?1.198, 95?% CI?=?1.118–1.285, P?=?3.4E?07), but not in Asians. Meta-analysis identified a significant negative association between SLE and the 2 allele of the rs2304256 polymorphism in the overall population (OR?=?0.808, 95?% CI?=?0.659–0.990, P?=?0.040), and a significant negative association was found in Europeans, but not in Asians.

Conclusions

This meta-analysis shows that the rs6445975 polymorphism of PXK and the rs2304256 polymorphism of TYK2 are associated with the development of SLE in Europeans.     

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).     

Associations between TNFSF15 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: A meta-analysis

Abstract

Aims: Several polymorphisms have been identified in TNFSF15, while their roles in the incidence of ulcerative colitis (UC) and Crohn's disease (CD) are conflicting. This meta-analysis was aimed to clarify the impact of these polymorphisms on UC and CD risk. Method: Databases were searched until 31 January 2014 for eligible studies on TNFSF15 polymorphisms. Data were extracted, and pooled odd ratios (ORs) as well as 95% confidence intervals (95% CIs) were calculated. Results: Fifteen studies with 8903 CD patients, 4687 UC patients and 12?606 controls were included. Except for rs4263839 polymorphism, significant associations were found between the rest six TNFSF15 polymorphisms and CD risk (rs3810936: OR?=?2.10, 95% CI, 1.47–3.00; rs6478108: OR?=?2.19, 95% CI, 1.53–3.13; rs4979462: OR?=?1.89, 95% CI, 1.42–2.52; rs6478109: OR?=?2.00, 95% CI, 1.39–2.88; rs7848647: OR?=?1.54, 95% CI, 1.15–2.06; rs7869487: OR?=?1.51, 95% CI, 1.06–2.17). And we found rs3810936, rs6478108 and rs6478109 polymorphism were significantly associated with UC risk (rs3810936: OR?=?1.19, 95% CI, 1.06–1.34; rs6478108: OR?=?1.16, 95% CI, 1.06–1.26; rs6478109: OR?=?1.16, 95% CI, 1.03–1.32). According to the subgroup analysis by ethnicity, except for rs4263839 in Caucasian and rs4979462 in Asian, all the rest investigated TNFSF15 polymorphisms were associated with CD risk and rs3810936 and rs7848647 polymorphism in Asian as well as rs6478108 polymorphism in Caucasian were associated with UC risk. Conclusion: This meta-analysis indicated that most of the seven TNFSF15 polymorphisms (except for rs4263839) were risk factors contributed to CD and UC susceptibility. The differences in ethnicity did not influence the risk obviously.     

Associations between interleukin-10 polymorphisms and susceptibility to psoriasis: a meta-analysis

Objective

The aim of this study was to determine whether three specific interleukin-10 (IL-10) polymorphisms confer susceptibility to psoriasis.

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -592 C/A polymorphisms and haplotypes of the IL-10-1082 G/A, -592 C/A, -819 C/T polymorphisms and psoriasis.

Results

A total of eight studies involving 1,018 psoriasis patients and 1,186 controls were considered in the meta-analysis. No association was found between psoriasis and the IL-10-1082 G allele in all study subjects [odds ratio (OR)?=?1.098, 95?% confidence interval (CI)?=?0.923?1.306, p?=?0.291] or between this allele and psoriasis in Europeans (OR?=?0.990, 95?% CI?=?0.809?1.214, p?=?0.925), but a significant association was found in Asians (OR?=?1.785, 95?% CI?=?1.144?2.76, p?=?0.011). Three polymorphisms at the promoter region of IL-10 (-1082 G/A, -819 C/T, -592 C/A) are known to be in complete linkage disequilibrium, but no association was found between the haplotype and psoriasis.

Conclusions

This meta-analysis shows that the IL-10-1082 G/A polymorphism confers susceptibility to psoriasis in Asians, and suggests that the IL-10 promoter -1082 polymorphism has an ethnicity-specific effect.     

MiR-196a2 rs11614913 T > C polymorphism and risk of esophageal cancer in a Chinese population

Background

Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. Methods: We conducted a hospital based case–control study to evaluate the genetic susceptibility of functional single nucleotide polymorphisms (SNPs) in the microRNAs on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The miR-196a2 rs11614913 T > C, miR-146a rs2910164 C > G, miR-499 rs3746444 T > C, miR-26a-1 rs7372209 C > T and miR-27a rs895819 T > C genotypes were determined using a custom-by-design 48-Plex SNPscan™ Kit and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Results

MiR-196a2 rs11614913 T > C polymorphism was associated with borderline statistically decreased risk of ESCC. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a borderline statistically decreased risk for ESCC (adjusted OR 0.72, 95% CI 0.50–1.03, p = 0.070). In stratification analyses, a significantly decreased risk of ESCC associated with the miR-196a2 rs11614913 T > C polymorphism was evident among women patients and patients who never smoking or drinking.

Conclusions

These findings indicated that functional polymorphism miR-196a2 rs11614913 T > C might contribute to decreased ESCC risk among women patients and patients who never smoking or drinking. However, our results were obtained with a limited sample size. Future larger studies with other ethnic populations and tissue-specific biological characterization are required to confirm current findings.     

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 CARD8 rs2043211 Polymorphism and Inflammatory Bowel Disease: A Meta-Analysis

Objective: The aim of this study was to determine whether caspase recruitment domain-containing protein 8 (CARD8) rs2043211 polymorphism was associated with susceptibility to inflammatory bowel disease (IBD).

Methods: Relevant studies were searched using PubMed and Embase up to February 2014. A meta-analysis was conducted on the association between rs2043211 polymorphism and IBD using: (1) allele contrast, (2) the dominant model, (3) the recessive model, and (4) homozygote contrast. The pooled estimated of risk was obtained by random-effects model or fixed-effects model. Publication bias was assessed by Egger’s test.

Results: Eight relevant articles with a total of 10?534 IBD patients [6785 Crohn’s disease (CD), 3713 ulcerative colitis (UC) and 36 indeterminate colitis (IC)] and 6755 healthy controls were included in the meta-analysis, which consisted of 12 studies, 12 for CD, 10 for UC, 2 for IC. There was no significant association between rs2043211 polymorphism and IBD, CD, and IC in overall population. However, stratified meta-analysis by ethnicity showed significant association between rs2043211 polymorphism and CD in the European population under the dominant model [odds ratio (OR)?=?1.210, 95% confidence interval (CI)?=?1.013–1.445, p?=?0.036] and homozygote contrast (OR?=?1.212, 95% CI?=?1.005–1.461, p?=?0.044).

Conclusions: Our meta-analysis results indicated significant association between rs2043211 polymorphism and the susceptibility to CD under the dominant model and homozygote contrast in the European population.     

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.     

NLRP3 gene is associated with ulcerative colitis (UC), but not Crohn’s disease (CD), in Chinese Han population

Objective

This study aimed to investigate whether NLRP3 is associated with IBD in Chinese Han population.

Methods

Three SNPs were genotyped using polymerase chain reaction with sequence-specific primers in 288 patients [232 Crohn’s disease (CD) patients, 56 ulcerative colitis (UC) patients] and 274 controls.

Results

In IBD group, the results showed no significant association. When subdivided to CD and UC, it showed in CD subgroup, there was no significant association. However, in UC subgroup, rs10754558 (P _allele = 0.015272, P _genotype = 0.029776, OR [95 % CI] = 0.604190[0.401200–0.909886]) and rs10925019 (P _allele = 0.013042, P _genotype = 0.037045, OR [95 % CI] = 2.022613[1.149854–3.557812]) have significant associations with UC. The G and T alleles were risk factors of the susceptibility of UC, the GG and TT genotypes may increase risk of this disease. Rs4925648 has no association with UC. The haplotypes analysis results showed as follow: for rs4925648–rs10925019, CC and TT are risk factors for UC (for CC, χ ² = 3.605, P = 0.057613, OR [95 % CI] = 1.645 [0.980–2.761], for TT, χ ² = 5.522, P = 0.018804, OR [95 % CI] = 0.426[0.205–0.884]), and for rs10754558–rs10925019, CT and GC haplotypes are risk factors for UC (for CT, χ ² = 3.545, P = 0.059739, OR [95 % CI] = 0.571[0.317–1.029], for GC, χ ² = 9.359, P = 0.002228, OR [95 % CI] = 1.904 [1.255–2.887]).

Conclusions

We first demonstrated that rs10754558 and rs10925019 are significantly associated with the susceptibility of UC, but not CD in Chinese Han population, suggesting that NLRP3 may play an important role in the pathogenesis of UC.     

Genetic polymorphisms of interleukin 17A and interleukin 17F and their association with inflammatory bowel disease in a Chinese Han population

Objective

Interleukin-17A and interleukin-17F (IL-17A and IL-17F) are candidate genes for chronic inflammatory disease. We investigated the association between IL17A/F gene polymorphisms and susceptibility to and clinical features of inflammatory bowel disease (IBD).

Methods

A total of 270 ulcerative colitis (UC) patients, 82 Crohn’s disease (CD) patients and 268 healthy controls were recruited in this study. Genomic DNA was extracted and analyzed for IL17A/F gene polymorphisms using ligase detection reaction allelic technology.

Results

Compared to the controls, the mutant allele C for IL17F rs763780 was significantly more common in CD patients [14.0 vs 8.4 %, P = 0.033, odds ratio (OR) 1.18, 95 % confidence interval (CI) 1.41–3.04] and was associated with the disease lesion location. This variant of IL17F rs763780 also had a weak correlation with the age of UC onset (P = 0.05, OR 0.97, 95 % CI 0.94–1.00). The IL17A (rs2275913, G-197A) variant had a weak association with the severity of disease: patients with the mutant allele A tended to suffer mild active UC. The haplotype (GGTT) of IL17A formed with four single nucleotide polymorphisms (rs2275913, rs8193037, rs8193038, and rs3804513) was associated with an increased risk of UC (P = 0.034, OR 4.58, 95 % CI 1.54–13.64).

Conclusions

The IL17F (rs763780, 7488T/C) variant was associated with an increased risk for the development of CD, and affected some clinical features of UC and CD. The IL17A (rs2275913, G-197A) variant had a weak association with the severity of UC. There was a risk haplotype in IL17A which could increase the risk of UC.     

Association of two polymorphisms rs2910164 in miRNA-146a and rs3746444 in miRNA-499 with rheumatoid arthritis: A meta-analysis

Background

It has been reported that two single nucleotide polymorphisms (SNPs) rs2910164 in miRNA-146a and rs3746444 in miRNA-499 might be associated with the susceptibility to rheumatoid arthritis (RA). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and RA risk.

Methodology/main results

A systematic search of studies on the association of two SNPs with susceptibility to RA was conducted in PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. A total of 6 case-control studies on rs2910164 and 3 studies on rs3746444 were included. Though no evidence of association was found between rs2910164 polymorphism and RA risk in all the genetic models, a trend of reduced risk could be drawn. (C versus G: OR = 0.93, 95% CI 0.82–1.05; GC versus GG: OR = 0.89, 95% CI 0.73–1.10; CC versus GG: OR = 0.84, 95% CI 0.64–1.10; GC/CC versus GG: OR = 0.89, 95% CI 0.73–1.08; CC versus GC/GG: OR = 0.94, 95% CI 0.77–1.14). A significant increased risk of RA was observed in the rs3746444 polymorphism in homozygote comparison, recessive comparison, and allele comparison, but there was insufficient data to fully confirm the association of RA and rs3746444 in miRNA-499.

Conclusions

MiRNA-146a rs2910164 polymorphism is not associated with RA risk, while miRNA-499 rs3746444 polymorphism is correlated with RA risk. However, the results of miRNA-499 rs3746444 should be interpreted with caution due to limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.     

Association of STAT4 rs7574865 with Susceptibility to Systemic Lupus Erythematosus in Iranian Population

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with complex genetic inheritance that affecting different organs and systems. STAT4 has been newly identified as a susceptible gene in the development of SLE. According to recent studies, STAT4 has been associated with SLE in various populations. We investigated whether STAT4 single nucleotide polymorphisms (SNPs) were associated with susceptibility and clinical features of SLE in Iranian patients. The study group comprised 280 patients with SLE and 281 sex-, age-, and ethnicity-matched healthy controls of Iranian ancestry. Two SNPs (rs7574865 and rs7601754) were genotyped using the TaqMan MGB Allelic Discrimination method. Our results showed a significant association betweenrs7574865 T allele (odds ratio (OR)?=?1.50, 95 % CI?=?1.18–1.92, P?=?0.002) and susceptibility to SLE. The rs7574865TT genotype (P?=?0.02, OR?=?1.94, 95 % CI?=?1.74–3.19) and GT genotype (P?=?0.008, OR?=?1.71, 95 % CI?=?1.19–2.45) showed a significant association with the risk of SLE in the Iranian population. We concluded that STAT4 rs7574865 is associated with SLE susceptibility in the Iranian population and this SNP might be a factor in the pathogenesis of SLE. However, further studies are required to investigate the mechanism by which polymorphisms in this gene lead to SLE.     

Association of genetic variants in estrogen receptor α with HCV infection susceptibility and viral clearance in a high-risk Chinese population

The purpose of this study was to test the hypothesis that genetic variants of estrogen receptor α (ERα) are associated with the outcomes of hepatitis C virus (HCV) infection. We genotyped the seven single nucleotide polymorphisms (SNPs) (rs2077647, rs9340799, rs2234693, rs1801132, rs9322354, rs2228480 and rs3798577) of ERα and conducted a case-control study in a high-risk Chinese population, including 429 HCV spontaneous clearance cases, 880 persistent infection cases and 1,174 uninfected controls. The C allele of rs2234693 was significantly associated with increased susceptibility to HCV infection [dominant model: adjusted odds ratio (OR)?=?1.377, 95 % confidence interval (CI) =1.126–1.778], and the risk effect remained significant among the younger (≤55 years) and hemodialysis subjects (all P?<?0.007). The other three SNPs variant genotypes also showed significant correlation with elevated risk of HCV infection in different strata (rs2077647 in males; rs9340799 in blood donors; rs1801132 in younger subjects; all P?<?0.007). It was also discovered that carriage of rs2228480 A allele was more prone to develop persistent HCV infection (dominant model: adjusted OR?=?1.203, 95 % CI?=?1.154–1.552), and the risk effect was more evident in females and blood donors (all P?<?0.007). Haplotype analyses (rs2077647, rs9340799 and rs2234693) showed that, compared with the most frequent haplotype TAT, CAC played a risk effect in subgroups of younger (P?=?3.24?×?10^?3) and male (P?=?5.51?×?10^?4), whereas CAT expressed a protective effect in females (P?=?2.27?×?10^?4) for HCV infection susceptibility. We first report that these SNPs (rs2077647, rs9340799, rs2234693, rs1801132 and rs2228480) in ERα can influence the outcomes of HCV infection in a high-risk Chinese population.     

The Polymorphisms K469E and G261R of Intercellular Adhesion Molecule-1 and Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

Objective: The aim of this study was to explore whether polymorphisms of intercellular adhesion molecule-1 (ICAM-1) are associated with susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC).

Methods: The authors conducted a meta-analysis on the associations between the polymorphisms K469E and G241R of ICAM-1 and susceptibility to CD and UC.

Results: A total of 8 studies with 801 patients with CD, 672 patients with UC, and 1,828 controls were included in the meta-analysis. The meta-analysis revealed no association between CD and the ICAM-1 469E allele among the subjects (OR?=?1.175, 95% CI?=?0.901–1.533, p?=?0.233). However, stratification by ethnicity indicated an association between the ICAM-1 469E allele and CD in Europeans (OR?=?1.425, 95% CI?=?1.013–2.002, p?=?0.042). Meta-analysis using the homozygosity also showed an association with CD in Europeans (OR?=?2.054, 95% CI?=?1.036–4.073, p?=?0.039). The meta-analysis revealed no association between UC and the ICAM-1 K469E polymorphism. No association between CD or UC and the ICAM-1 G241R polymorphism was observed.

Conclusions: This meta-analysis demonstrates that the ICAM-1 K469E polymorphism may be associated with susceptibility to CD in Europeans, but no association was found between ICAM-1 K469E and UC. In contrast, the G241R polymorphism was not found to be associated with susceptibility to either CD or UC.     

CD38 Gene polymorphisms and susceptibility to B cell chronic lymphocytic leukemia

CD38 was suggested to be not only a prognostic marker but also a key element in the pathogenetic network underlying chronic lymphocytic leukemia (CLL). We aimed at determining whether polymorphisms of CD38 gene influence the risk of B-CLL and thus analyzed two potentially functional CD38 single nucleotide polymorphisms (SNPs), rs6449182 (184 C>G), and rs1800561 (418 C>T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assays in a study including 70 B-CLL patients and 70 age- and gender-matched controls. Our results demonstrated that the homozygous mutant genotypes of the two studied SNPs (GG and TT) showed a significantly higher risk of B-CLL compared with the homozygous wild types (p value?<?0.001, OR?=?2.813, 95% CI?=?1.898–4.168 and p value?=?0.011, OR?=?2.250, 95%CI?=?1.707–2.96, respectively). In addition, G and T carriers had more advanced clinical stage (p value?<?0.001). Also, a significant association was demonstrated between higher proportions of CD38-positive cells and carriers of G and T alleles (p value?<?0.001). Our data suggest that the risk of B-CLL carcinogenesis may be influenced by CD38 SNPs [rs6449182 (184 C>G) and rs1800561 (418 C>T)].