No association between IL-1β −31 C/T polymorphism and the risk of duodenal ulcer: A meta-analysis of 3793 subjects

The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β −31 C/T polymorphism and duodenal ulcer (DU). Systematic searches of electronic databases Embase, PubMed and Web of Science were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were applied. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. A total of 12 studies including 1151 cases and 2642 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β −31 C/T polymorphism and DU (allelic model: OR = 0.96, 95%CI = 0.86–1.07; additive model: OR = 0.85, 95%CI = 0.67–1.07; dominant model: OR = 0.95, 95%CI = 0.81–1.13; and recessive model: OR = 0.95, 95%CI = 0.79–1.15). Significant association was found in additive model for PB subgroup (OR = 0.65, 95%CI = 0.44–0.96) and recessive model for non-Asian subgroup (OR = 0.72, 95%CI = 0.52–0.99). In conclusion, our meta-analysis suggested that there was no evidence of significant association between IL-1β −31 C/T polymorphism and DU with or without Helicobacter pylori infection in overall population, whereas significant association was found by subgroup analyses which showed protective effect of C/C genotype against DU risk.     

Association between interleukin-1β C (3953/4)T polymorphism and chronic periodontitis: Evidence from a meta-analysis

The aim of this study was to perform a meta-analysis to evaluated the association between interleukin-1β (IL-1β) C(3953/4)T polymorphism and chronic periodontitis (CP). Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase and Web of Science. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy–Weinberg equilibrium (HWE) or high quality (score ? 7). Data analyses were carried out by Stata 11.0. There were significant associations between IL-1β C(3953/4)T polymorphism and CP (for T allele vs. C allele: OR = 1.30, 95%CI = 1.05–1.60, p = 0.02; for T/T vs. C/C: OR = 1.66, 95%CI = 1.12–2.45, p = 0.01; for C/T + T/T vs. C/C: OR = 1.28, 95%CI = 0.99–1.65; and for T/T vs. C/T + C/C: OR = 1.62, 95%CI = 1.15–2.29, p = 0.006). When stratified by ethnicity, statistically significantly elevated risk was found for Caucasians, but not for Asians. When stratified by study design, evidences of significant association was observed between IL-1β C(3953/4)T polymorphism and CP in both population-based studies and hospital-based studies. This meta-analysis indicates that there is strong evidence for association between IL-1β C(3953/4)T polymorphism and CP.     

Association of insulin gene variable number of tandem repeats regulatory polymorphism with polycystic ovary syndrome

The present meta-analysis aimed to investigate the association between insulin gene variable number of tandem repeats (INS VNTR) and polycystic ovary syndrome (PCOS). Systematic searches of electronic databases, reference lists of included articles, and the abstracts presented at related scientific societies meetings were performed. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were applied. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. A total of 9 studies including 1075 PCOS patients and 2878 controls were included in the meta-analysis. There were evidence of statistical significant association between INS VNTR and PCOS in allelic model (OR = 1.25, 95% CI = 1.08–1.43, P = 0.002) and dominant model (OR = 1.34, 95% CI = 1.11–1.63, P = 0.003) but not in additive model (OR = 1.38, 95% CI = 0.93–2.04, P = 0.11) and recessive model (OR = 1.26, 95% CI = 0.96–1.65, P = 0.09). No significant publication bias was shown by funnel plots and Egger’s regression tests. In conclusion, our meta-analysis suggests that the III allele of INS VNTR is associated with increased risk of PCOS.     

Meta-analysis of FKBP5 gene polymorphisms association with treatment response in patients with mood disorders

The aim of our study was to assess the association between FKBP5 gene polymorphisms and treatment response in patients with mood disorders using a meta-analysis. Eight separate studies that included data from 2199 subjects were identified. Meta-analysis was performed for three FKBP5 gene polymorphisms (rs1360780, rs3800373, and rs4713916). A significant association of FKBP5 gene rs4713916 polymorphism and response rate was found in patients with mood disorders (Overall: A versus G: OR = 1.28, 95%CI = 1.06–1.53, P = 0.01; GA + AA versus GG: OR = 1.32, 95%CI = 1.05–1.67, P = 0.02. Caucasian: A versus G: OR = 1.28, 95%CI = 1.06–1.55, P = 0.01; GA + AA versus GG: OR = 1.33, 95%CI = 1.04–1.70, P = 0.02). However, we did not detect the association between FKBP5 gene rs1360780 and rs3800373 polymorphisms and treatment response in patients with mood disorders (P > 0.05). This meta-analysis demonstrates that treatment response in patients with mood disorders is associated with FKBP5 gene rs4713916 polymorphism, but not rs1360780 and rs3800373.     

CD226 Gly307Ser association with multiple autoimmune diseases: A meta-analysis

Background

Recently, there has been increasing evidence shown that a non-synonymous exchange (Gly307Ser/rs763361) of the CD226 gene on chromosome 18q22 is linked to several autoimmune diseases (ADs) including type 1 diabetes (T1D), celiac disease (CED), rheumatoid arthritis (RA), multiple sclerosis (MS), Grave’s disease, Wegener’s granulomatosis (WG), psoriasis, and primary sicca syndrome (pSS). Taking into consideration that different autoimmune diseases may share some common pathogenic pathways and in order to assess the overall relationship between CD226 Gly307Ser (rs763361) polymorphism and multiple autoimmune diseases, we performed this meta-analysis.

Method

All eligible case-control studies were searched in the US National Library of Medicine’s PubMed and Embase database. Crude odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association.

Results

7876 cases and 8558 controls from 7 published studies which were selected from 149 articles identified by a search of the US National Library of Medicine’s PubMed and Embase databases for the period up to 25th April 2012. The total OR for ADs associated with the T allele was 1.19 (95%CI = 1.12–1.27) by random effects model. Significantly increased risks were also observed in the South American (OR = 1.72, 95%CI = 1.34–2.20), Asian (OR = 1.46, 95%CI = 1.01–2.10), and European (OR = 1.29, 95%CI = 1.07–1.58). Similarly, significant associations were observed in two genetic models (OR = 1.41, 95%CI = 1.23–1.62 in a codominant model; OR = 1.33, 95%CI = 1.18–1.50 in a recessive model).

Conclusion

This meta-analysis provided evidence that CD226 Gly307Ser (rs763361) is significantly associated with the risk of multiple autoimmune diseases.     

Meta-analysis of the relationship between 14bp insertion/deletion polymorphism of HLA-G gene and susceptibility to systemic lupus erythematosus

We performed a meta-analysis to examine the relationship between the human leukocyte antigen-G (HLA-G) 14 base pairs sequence (14bp) insertion (ins)/deletion (del) polymorphism to systemic lupus erythematosus (SLE). Eligible studies were extracted in PubMed, Embase, Cochrane Library and CNKI (Chinese) up to March 31, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the strength of the association. Finally, 7 studies with 1864 cases and 2259 controls were involved in this meta-analysis. Overall, the HLA-G 14bp ins/del polymorphism was significantly associated with SLE susceptibility (ins vs. del: OR = 1.179, 95%CI = 1.037–1.341, P = 0.012; ins/ins vs. del/del: OR = 1.394, 95%CI = 1.153–1.684, P = 0.001; ins/del vs. del/del: OR = 1.199, 95%CI = 1.041–1.382, P = 0.012; ins/ins + ins/del vs. del/del: OR = 1.252, 95%CI = 1.097–1.430, P = 0.001). When stratified by ethnicity, significance was found in Asians (ins/ins vs. del/del: OR = 1.326, 95%CI = 1.001–1.756, P = 0.049) and Caucasians (ins/ins vs. del/del: OR = 1.454, 95%CI = 1.126–1.878, P = 0.004; ins/del vs. del/del: OR = 1.288, 95%CI = 1.051–1.579, P = 0.015; ins/ins + ins/del vs. del/del: OR = 1.340, 95%CI = 1.106–1.623, P = 0.003). Our results suggest that the HLA-G 14bp insertion allele might act as an increased risk against SLE. Besides, this is the first meta-analysis to report an association between the HLA-G 14bp ins/del polymorphism and SLE. Larger and well-designed studies are needed to further confirm these findings.     

Association of ADIPOQ polymorphisms with obesity risk: A meta-analysis

Background

The association between ADIPOQ polymorphisms and the risk of obesity remains controversial. We perform a comprehensive meta-analysis to clarify the current understanding of this association.

Methods

We searched for relevant studies in PubMed, Embase and Cochrane library before February 2014. The strengths of the association between ADIPOQ polymorphisms and obesity risk were estimated by odds ratios (OR) with 95% confidence intervals (CI).

Results

Eighteen case–control studies analyzing four SNPs (rs17300539, rs266729, rs1501299 and rs2241766) of ADIPOQ gene were eligible for the present meta-analysis. The pooling results showed that rs17300539 (2GG+GA vs. 2AA+GA: OR = 0.78, 95%CI = 0.69–0.89) and rs1501299 (2GG+GA vs. 2AA+GA: OR = 0.89, 95%CI = 0.80–0.98) were associated with obesity risk in Caucasian ethnicity. The rs266729 were associated with obesity risk in Asian ethnicity (2CC+CG vs. 2GG+GCG: OR = 0.77, 95%CI = 0.65–0.92). However, there were no associations between rs2241766 and the obesity risk (P > 0.05). No publication bias was found among these studies (all P > 0.05).

Conclusions

This study suggests that ADIPOQ rs17300539 and rs1501299 are associated with risk of obesity in Caucasian ethnicity, and the rs266729 is associated with obesity risk in Asian ethnicity. However, there is no association between rs2241766 and obesity risk.     

NEDD9 rs760678 polymorphism and the risk of Alzheimer's disease: A meta-analysis

The NEDD9 rs760678 polymorphism has been extensively investigated for association to Alzheimer's disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of NEDD9 rs760678 polymorphism and AD risk by using meta-analysis. Systematic searches of electronic databases Pubmed and Embase, as well as hand searching of the references of identified articles were performed. Statistical analyses were performed using software Revman 4.2 and STATA 11.0. A total of 4436 cases and 4420 controls in 11 case–control studies were included. The results indicated that the homozygote GG had a 13% decreased risk of AD, when compared with the C allele carriers (CC + CG) (OR = 0.87, 95%CI = 0.77–0.99, P = 0.04 for GG vs. CG + CC). In the subgroup analysis by ethnicity, significant decreased risk was associated with homozygote GG or G allele carriers in Caucasians (OR = 0.84, 95%CI = 0.74–0.96, P = 0.008 for GG vs. CG + CC; OR = 0.79, 95%CI = 0.69–0.91, P = 0.001 for GG vs. CC; OR = 0.90, 95%CI = 0.84–0.96, P = 0.002 for G vs. C), but not in Asians. This meta-analysis suggests that the GG genotype of NEDD9 rs760678 polymorphism would be a protective factor for AD in Caucasians but not in Asians. To further evaluate the effect of gene–gene and gene–environmental interactions between NEDD9 rs760678 polymorphism and the risk of AD, more studies with larger number of subjects are required.     

Alleles and genotypes of polymorphisms of IL-18, TNF-α and IFN-γ are associated with a higher risk and severity of hepatocellular carcinoma (HCC) in Brazil

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver. We evaluated the association of alleles and genotypes of polymorphisms of IL-18 (-607C/A and -137G/C), IFN-γ (+874T/A) and TNF-α (-238G/A and -308G/A) with the risk and severity of HCC. One-hundred-and-twelve patients with HCC and 202 healthy controls were studied. Single nucleotide polymorphisms (SNPs) were amplified by PCR with specific primers and the products were submitted to polyacrylamide gel electrophoresis and stained with silver. We evaluated tumor presentation, tumor size and presence of metastasis. Significant higher risk of HCC was associated with: alleles IL-18 -607^∗A (P = 0.0235; OR = 1.48; 95%CI = 1.06–2.08); TNF-α -238^∗A (P = 0.0025; OR = 2.12; 95%CI = 1.32–3.40) and TNF-α -308^∗A (P = 0.0351; OR = 1.82; 95%CI = 1.07–3.08); and genotypes IL-18–607AA (P = 0.0048; OR = 3.03; 95%CI = 1.40–6.55); TNF-α -238GA (P = 0.0011; OR = 2.44; 95%CI = 1.45–4.12); and TNF-α -308GA (P = 0.0031; OR = 2.51; 95%CI = 1.39–4.51). Significant association was found between multinodular HCC and IL-18 -607^∗C allele (P = 0.029; OR = 2.40, 95%CI: 1.09–5.28), and IL-18 -607CC genotype (P = 0.028; OR = 3.5, 95%CI: 1.24–9.86). Diffuse HCC was significantly associated with IFN-γ +874TA genotype (P = 0.044; OR = 3.6, 95%CI: 1.03–12.47). The IL-18 -137^∗C allele showed a significant association with the presence of metastasis. Thus, IL-18 -607^∗A and TNF-α (-238^∗A and -308^∗A) alleles may confer susceptibility to HCC, while IL-18 -607^∗C and -137^∗C alleles more severe disease.     

Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

The study determined whether interleukin-10 (IL-10) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).

Methods

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

Results

A total of 19 studies involving 2828 SLE patients and 4008 controls were considered in the meta-analysis. Meta-analysis of the IL-10-1082 G/A polymorphism revealed an association between SLE and the IL-10-1082 G allele (odds ratio [OR] = 1.158, 95% confidence interval [CI] = 1.051–1.276, p = 0.003). Stratification by ethnicity indicated an association between the IL-10-1082 G allele and SLE in Europeans (OR = 1.160, 95% CI = 1.039–1.296, p = 0.008). Meta-analysis stratified by ethnicity produced an association between the IL-10-819 C allele and SLE in Asians (OR = 1.308, 95% CI = 1.030–1.619, p = 0.027). Meta-analysis of the homozygous GCC/GCC haplotype failed to show a significant association with SLE in Europeans (OR = 1.223, 95% CI = 0.981–1.526, p = 0.074). However, meta-analysis of the GCC haplotype revealed a significant association with RA in all study subjects (OR = 1.402, 95% CI = 1.001–1.964, p = 0.049). Stratification by ethnicity indicated an association between the GCC haplotype and SLE in Europeans (OR = 1.656, 95% CI = 1.087–2.523, p = 0.019), but not in Asians (OR = 1.100, 95% CI = 0.703–1.721, p = 0.677). Meta-analysis of homozygous ATA/ATA haplotype failed to show a significant association with SLE in overall and European groups. However, meta-analysis of the ATA haplotype revealed a significant association with SLE in all study subjects (OR = 1.516, 95% CI = 1.039–2.213, p = 0.031) and Asians (OR = 2.580, 95% CI = 2.086–3.192, p < 1 × 10⁻⁹), but not in Europeans (OR = 1.233, 95% CI = 0.816–1.862, p = 0.320).

Conclusions

This meta-analysis suggests that the IL-10 polymorphisms confer susceptibility to SLE in Europeans and in Asians.     

A meta-analysis about the association between −1082G/A and −819C/T polymorphisms of IL-10 gene and risk of type 2 diabetes

The present meta-analysis was conducted to investigate the association between the −1082G/A and −819C/T polymorphisms of the IL-10 gene and risk of type 2 diabetes mellitus (T2DM). Relevant articles were identified by searching PubMed, Embase, and Web of Science. Pooled odds ratios (ORs) were used to assess the strength of the association between target polymorphisms and the risk of T2DM. Significant associations between the −1082G/A polymorphism and T2DM were found for the allele contrast (OR = 0.90, 95% CI: [0.83, 0.98], P = 0.02), homozygote contrast (OR = 0.82, 95% CI: [0.69, 0.97], P = 0.02), and recessive genetic model (OR = 0.85, 95% CI: [0.74, 0.96], P = 0.01). However, no significant association was found for the dominant genetic model (OR = 0.91, 95% CI: [0.80, 1.05], P = 0.08). The association between −819C/T polymorphism and T2DM was significant for the allele contrast (OR = 0.73, 95% CI: [0.64, 0.84], P < 0.01); however, no significant associations were found for −819C/T in the homozygote contrast (OR = 1.01, 95% CI: [0.38, 2.67], P = 0.99), dominant genetic model (OR = 0.94, 95% CI: [0.50, 1.77], P = 0.86), and recessive genetic model (OR = 0.92, 95% CI: [0.50, 1.68], P = 0.78). No significant publication bias was detected. This meta-analysis suggests that allele A of −1082G/A and allele C of −819C/T in the IL-10 gene have potentially protective effects in terms of risk of T2DM.     

Associations between interleukin 1 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

This study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL1A, IL1B, and IL1 receptor antagonist (IL1RN) polymorphisms and SLE.

Results

A total of 15 studies involving 1956 SLE cases and 2347 controls were included in the meta-analysis. The meta-analysis showed an association between SLE and the IL1A −889 T allele in the overall population and Europeans (OR = 0.858, 95% CI = 0.737–0.986, p = 0.032; OR = 0.827, 95% CI = 0.687–0.994, p = 0.043). Meta-analysis of the IL1RN polymorphism revealed an association with SLE in all study subjects (OR for IL1RN^∗2 = 1.539, 95% CI = 1.266–1.871, p = 1.5 × 10⁻²) and in Europeans and Asians (OR = 1.483, 95% CI = 1.187–1.852, p = 0.001; OR = 1.787, 95% CI = 1.167–2.736, p = 0.008). No associations were found between SLE and the IL1B −511 C/T, 3953 C/T, and IL1A +4845 G/T polymorphisms.

Conclusions

This meta-analysis suggests IL1A −889 C/T polymorphism is associated with susceptibility to SLE in Europeans, and that the IL1RN^∗2 allele is associated with susceptibility to SLE in Europeans and Asians.     

Association between interleukin-8 gene −251 T/A polymorphism and the risk of peptic ulcer disease: A meta-analysis

It remains controversial regarding the association between interleukin-8 (IL-8) gene −251 T/A polymorphism and peptic ulcer disease (PUD) risk. Thus, a large-scale meta-analysis evaluating the precise association between this gene variant and PUD risk is required. We searched the PubMed, Embase, Web of Science, and Google Scholar until April 25, 2012. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Stata 11.0. A total of eight studies (3105 subjects) were included in this meta-analysis. Overall, no significant association was found between IL-8 gene −251 T/A polymorphism and PUD risk (for A allele vs. T allele: OR = 1.17, 95% CI = 0.97–1.41, p = 0.094; for A/A vs. T/T: OR = 1.33, 95% CI = 0.94–1.90, p = 0.108; for A/A vs. A/T + T/T: OR = 1.22, 95% CI = 0.97–1.52, p = 0.083; for A/A + A/T vs. T/T: OR = 1.26, 95% CI = 0.95–1.67, p = 0.113). However, in the subgroup analyses by ethnicity, H. pylori infection and the subtype of PUD, significant associations were found between IL-8 gene −251 T/A polymorphism and PUD risk in Asians, H. pylori+, duodenal ulcer disease (DUD) and gastric ulcer disease (GUD), respectively. In summary, the present meta-analysis suggests that IL-8 gene −251 T/A polymorphism is associated with increased PUD risk among Asians, and especially for the subgroups of H. pylori+, DUD and GUD.     

Polymorphisms of interleukin 6 and interleukin 10 in Egyptian people with Behcet's disease

Cytokines play critical roles in the pathogenesis of Behçet's disease (BD). They mediated many of the effectors and regulatory functions of immune and inflammatory responses. Many studies have linked Interleukin-6 (IL-6) and Interleukin-10 (IL-10) pathologically to BD. Thus, this study aimed to investigate the associations between IL-6 and IL-10 promoter single-nucleotide polymorphisms (SNPs) and the susceptibility to BD and their implication on plasma levels. We genotyped IL-6 −174 G/C (rs1800795) using Mutagenically Separated Polymerase Chain Reaction PCR (MS-PCR) and IL-10 −1082 G/A (rs1800896) and −819 C/T (rs1800871) using Sequence Specific Primer PCR (SSP-PCR) in 87 Egyptian patients and 97 controls. The plasma levels of IL-6 and IL-10 were measured using Enzyme-linked Immunosorbent Assay (ELISA). Significant increase in the frequency of −1082 GG genotype (P < 0.05, OR = 2.25, 95%CI = 1.03–4.91) and significant decrease in the frequency of −1082 GA genotype (P < 0.05, OR = 0.53, 95%CI = 0.29–0.96) was demonstrated in BD patients compare to controls. Patients with genital ulcer had significantly lower frequency of −1082 GG (P < 0.05, OR 0.2, 95% CI = 0.04–0.99) and G allele (P < 0.05, OR = 0.28, 95%CI = 0.08–0.93), while patients with ocular manifestations had significantly higher frequency of −1082 G allele (P < 0.01, OR = 2.28, 95%CI = 1.19–4.36). BD patients had significantly higher level of IL-6 (P < 0.001) and significantly lower level of IL-10 (P < 0.001) compared to controls. The changes in the level of cytokines were independent of any genotype of IL-6 or any genotype/haplotype of IL-10. Patients with active disease state had significantly higher level of IL-6 compared to patients in remission (P < 0.05). In conclusion, our preliminary study indicates that the polymorphism at IL-10 −1082 G/A may play a role in BD susceptibility. The significant increase in IL-6 level and the significant decrease in IL-10 level in BD patients were independent of any particular genotype in IL-6 or any particular genotype/haplotype in IL-10.     

Toll-like receptor 6 gene polymorphisms increase the risk of bovine tuberculosis in Chinese Holstein cattle

Our present study aimed to investigate the effect of four SNPs (G1793A, C1859A, A1980G, G1934A) in toll-like receptor 6 (TLR6) on bovine tuberculosis (bTB) resistance in a case–control study. A total of 603 Chinese Holstein cattle (264 from a dairy farm of Henan province, 339 from Hubei province) were selected to analyze the genotype of TLR6 gene by PCR-RFLP. Genotype frequencies of C1859A and A1980G site differed significantly between bTB-infected and non-infected cows (χ² = 6.062, P = 0.048 and χ² = 6.749, P = 0.034, respectively). Relative risk of tuberculosis incidence result showed that genotypes of AA or CA had greater relative risk (OR = 2.730, 95%CI = 0.869–8.573; OR = 1.547, 95CI% = 0.803–2.982, respectively) than those with genotype CC at C1859A site between bTB-infected and non-infected animals. Genotypes of GG or GA had greater relative risk (OR = 2.986, 95%CI = 1.245–7.165; OR = 1.582, 95%CI = 0.734–3.409, respectively) than those with genotype AA at A1980G site. No significant association can be inferred from G1793A and G1934A polymorphism site. The present study suggests that variants in the TLR6 gene are associated with susceptibility to bTB and the TLR6 gene may be considered as a candidate gene for bTB resistance.     

Association of rs12979860 and rs8099917 polymorphisms near IL28B with SVR in hepatic allograft recipients with HCV recurrence undergoing PEG-IFN/RBV therapy: A meta-analysis

The association of rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) near IL28B with sustained virological response (SVR) in hepatic allograft recipients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV) for recurrent hepatitis C virus (HCV) infection remains inconclusive. We therefore performed a meta-analysis to estimate this association. A search of the literature published prior to November 1, 2013, was conducted using various databases. Eleven eligible studies were included in the meta-analysis. The pooled results revealed that rs12979860 genotype CC in the recipient, donor, and recipient/donor pair was significantly related to high SVR in the recipients (recipient: odds ratio [OR] = 3.06, 95% confidence interval [CI] = 2.18–4.30; donor: OR = 2.65, 95% CI = 1.83–3.85; recipient/donor pair: OR = 6.05, 95% CI = 3.16–11.58). A similar association was observed with rs8099917 genotype TT (recipient: OR = 3.84, 95% CI = 2.37–6.22; donor: OR = 2.44, 95% CI = 1.12–5.28; recipient/donor pair: OR = 5.43, 95% CI = 2.51–11.75). These results suggest that rs12979860 genotype CC and rs8099917 genotype TT contribute to a high SVR in the recipient after antiviral treatment.     

Association of CTLA-4 variants with susceptibility to inflammatory bowel disease: A meta-analysis

Objective

The aim of this study was to determine whether CTLA-4 gene variants were associated with susceptibility to inflammatory bowel disease (IBD).

Methods

Meta-analysis was conducted on the association between CTLA-4 variants and IBD using: (1) allelic contrast, (2) the recessive model, and (3) the dominant model.

Results

A total of 9 relevant studies including 1739 Crohn’s disease (CD) cases, 10 relevant studies containing 1017 ulcerative colitis (UC) cases and 2685 healthy controls were involved in this meta-analysis. Overall, CTLA-4+49A/G, −318C/T and CT60 variants were not associated with IBD susceptibility in all genetic models (P > 0.05). Stratification by ethnicity indicated a significant association between the CTLA-4+49A/G variant and CD in Caucasian group (GG vs. GA + AA: OR = 0.723, 95% CI = 0.564–0.926, P = 0.010). In Asian group, meta-analysis showed a significant association between the CTLA-4 CT60 variant and UC (AA vs. AG + GG: OR = 0.375, 95% CI = 0.163–0.861, P = 0.021).

Conclusions

Based on the published literature, this meta-analysis suggests that the CTLA-4+49A/G variant may be related to CD susceptibility in Caucasians, and the CTLA-4 CT60 variant may be associated with UC susceptibility in Asians.     

Interleukin 6 −174G>C polymorphism and cancer risk: Meta-analysis reveals a site dependent differential influence in Ancestral North Indians

In our earlier studies, single nucleotide polymorphisms (SNPs) associated with anti-inflammatory cytokines were found to influence risk for breast cancer in western Indian women. Analysis of Interleukin 6 (IL-6) −174G>C polymorphism in this cohort (patients = 182; controls = 236) suggested a protective role for IL-6 −174C allele associated with the lower expression of the cytokine (OR = 0.54; 95% CI 0.32–0.89, dominant model). Together these observations suggested that in comparison to Caucasians, inflammation associated-cytokine gene polymorphisms may have higher influence on risk for cancer in this population. To examine this possibility we analyzed data assessing influence of Interleukin 6 (IL-6) −174G>C polymorphism on risk for various cancers. Overall, there was a marginally higher risk for rare allele homozygotes compared to wild type homozygotes (OR = 1.07; 95% CI 1.00–1.15). Increased risks for genitourinary cancers and for skin cancer were also indicated. The ethnicity based analysis indicated a protective effect of the minor allele in Ancestral North Indians (OR = 0.73; 95% CI 0.55–0.97). Site by ethnicity analysis once again revealed a significant protection against breast cancer (OR = 0.51; 95% CI = 0.37–0.70; dominant model) but an opposite influence on the risk of genitourinary malignancies (OR = 2.51; 95% CI 1.59–3.96; recessive model) in this population alone. The observations imply that contribution of IL-6 to inflammation or effector immunity may depend on the site of malignancy. Assessment of available data in relation to prognosis in breast cancer patients also revealed trends that are compatible with the observations of the meta-analysis. Thus, IL-6 −174G>C polymorphism clearly represents a potential modulator of risk for malignant disorders with ethnicity and site dependent trends. The results also support the possibility of higher influence of inflammation related cytokine gene polymorphisms on the risk for cancers in Ancestral North Indians.     

Association between CTLA-4 polymorphisms and susceptibility to Celiac disease: A meta-analysis

Objective

The study explored whether cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphisms confer susceptibility to Celiac disease (CD).

Methods

A meta-analysis was conducted on the associations between the CTLA-4 CT60 A/G, +49 A/G, −318 C/T polymorphisms and CD using allele contrast, a recessive model, a dominant model, and homozygote contrast.

Results

Thirteen separate comparison studies were considered in the meta-analysis consisting of 5072 patients with CD and 13,462 controls. All subjects were Europeans. Meta-analysis of the CTLA-4 CT60 A/G polymorphism showed an association between CD and the CTLA-4 CT60 G allele in all subjects [Odds ratio (OR) = 1.160, 95% Confidence interval (CI) = 1.104–1.219, p < 1.0 × 10⁻⁹). Meta-analysis using the recessive model also revealed an association between CD and the CTLA-4CT60 GG genotype (OR = 1.331, 95% CI = 1.093–1.620, p = 0.004). Furthermore, analyses using the dominant model and homozygote contrast showed the same pattern as that shown by the CTLA-4CT60 G allele. Meta-analysis of the CTLA-4 +49 A/G polymorphism showed no association between CD and the CTLA-4 +49 G allele in all subjects (OR = 0.992, 95% CI = 0.872–1.129, p = 0.907). Meta-analysis using the recessive, dominant model, and homozygote contrast showed the same pattern as that shown by the CTLA-4 +49 Gallele. Meta-analysis of the CTLA-4 −318 C/T polymorphism showed no association between CD and the CTLA-4 −318 T allele in all subjects (OR = 1.018, 95% CI = 0.813–1.275, p = 0.877).

Conclusions

The CTLA-4 CT60 A/G polymorphism was associated with CD susceptibility, but no association was found between CTLA-4 +49 A/G and −318 C/T polymorphisms and CD in Europeans.     

Association between apolipoprotein E gene polymorphism and the risk of vascular dementia: A meta-analysis

It remains controversial regarding the association between Apolipoprotein E (ApoE) gene polymorphism and the risk of vascular dementia (VaD). The present meta-analysis was performed to derive a more precise estimation of the relationship. The meta-analysis was performed by searching PubMed, Embase and Web of Science databases. A total of 29 studies included 1763 VaD cases and 4534 controls were identified. The results showed evidence for significant association between ApoE ?4 mutation and VaD risk (for ?3/?4 vs. ?3/?3: OR = 1.65, 95% CI = 1.40–1.94, p-value < 0.00001; for ?4/?4 vs. ?3/?3: OR = 3.17, 95% CI = 2.09–4.80, p-value < 0.00001; for ?4 allele vs. ?3 allele: OR = 1.72, 95% CI = 1.40–2.12, p-value < 0.00001). The similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta-analysis suggests an association between ApoE ?4 mutation and increased risk of VaD. However, due to the small sample size in most of the included studies and the selection bias existed in some studies, the results should be interpreted with caution.