Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis

A number of studies have tested the association of the complement receptor 1 (CR1) and Interleukin-10 (IL10) polymorphisms with systemic lupus erythematosus (SLE), but reported conflicting results. The aim of the study is to explore whether the CR1 and IL10 genes are associated with SLE susceptibility. We surveyed studies on the CR1 and IL10 polymorphisms and SLE using comprehensive Medline search and review of the references. A meta-analysis was conducted in a fixed effects model or random effects model based on between-study heterogeneity. Eighteen comparisons from 13 studies were included in the CR1 meta-analysis and a total of 16 separate comparisons were used for the IL10 meta-analysis. The CR1 meta-analysis showed no significant association of the CR1 functional polymorphisms with SLE. In contrast, the S structural variant of the CR1 showed a significant association (OR=1.544, 95% CI, 1.217–1.959, P<0.001). Stratification by ethnicity indicated that the CR1 S variant was associated with SLE in Caucasians (OR=1.667, 95% CI, 1.193–2.357, P=0.003). The IL10 meta-analysis showed a significant association between SLE and the G11 allele of IL10.G (OR=1.279, 95% CI; 1.027–1.593, P=0.028) in whole populations, and IL10 promoter −1082G allele was associated with SLE in Asians (OR=1.358, 95% CI; 1.015–1.816, P=0.039). In conclusion, the CR1 meta-analysis revealed the association of the S structural variant of the CR1 with SLE and the IL10 meta-analysis showed the association of IL10.G11 allele and SLE in whole populations and the association between promoter -A1082G polymorphism and SLE in Asians.     

Association between the CTLA-4 +49 A/G polymorphism and susceptibility to rheumatoid arthritis: a meta-analysis

The aim of this study was to explore whether the cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 A/G polymorphism confers susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between CTLA-4 +49 A/G polymorphism and RA using; 1) allele contrast, 2) the recessive model, 3) the dominant model, and 4) an additive model. A total of 19 studies, 5,752 RA patients and 5,508 controls, encompassing 9 Caucasian, 8 Asian, 1 Mexican, and 1 Tunisian population were included in this meta-analysis. Ethnicity-specific meta-analysis was performed on Caucasian and Asian populations. Meta-analysis of the CTLA-4 +49 A/G polymorphism revealed an association between RA and the CTLA-4 +49 G allele in all 11,260 study subjects (odds ratio (OR) 1.118, 95% confidence interval (CI) 1.033–1.210, P = 0.005). Stratification by ethnicity showed an association between the CTLA-4 +49 G allele and RA in Asians (OR 1.164, 95% CI 1.056–1.283, P = 0.002), but no evidence of an association in Caucasians (OR 1.085, 95% CI 0.973–1.209, P = 0.431). Furthermore, associations were found between RA and the CTLA-4 +49 A/G polymorphism in Asians using the dominant and additive models, but not using the recessive model. On the other hand, no association was found between RA and the CTLA-4 +49 A/G polymorphism using the recessive, dominant, or additive models in Caucasians. This meta-analysis demonstrates that the CTLA-4 +49 A/G polymorphism confers susceptibility to RA in Asians, but not in Caucasians.     

Meta-analysis of the association of CTLA-4 exon-1 +49A/G polymorphism with rheumatoid arthritis

Rheumatoid arthritis (RA) is a common autoimmune disease. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a highly suspected candidate gene for RA susceptibility. However, association studies on the polymorphism of CTLA-4 exon-1 +49A/G in RA have shown conflicting results. Therefore, we performed a meta-analysis to better assess the purported association. In order to look for ethnic effect, we performed subgroup meta-analysis in populations of European descent and Asian descent. Meta-regression analysis was also performed to explore the possible heterogeneity between the two subgroups. Ten studies (11 comparisons) with the CTLA-4 exon-1 +49A/G genotyping on 2,315 patients with RA and 2,536 controls were selected for our meta-analysis. Overall, the fixed-effects odds ratio (OR) for the G versus A allele was 1.11 (P=0.02, 95% confidence interval (CI) 1.02–1.21), with no between-study heterogeneity. Subgroup and meta-regression analysis according to the ethnicity (European or Asian) demonstrated different scenarios concerning the CTLA-4 exon-1 +49A/G polymorphism’s role in RA susceptibility for the two different subgroups. No effect of G on susceptibility was seen in European descent (five comparisons; OR=1.04, P=0.30, 95% CI 0.95–1.19; no significant between-study heterogeneity). However, there is a significant association in Asian descent under both fixed [OR=1.21, 95% CI (1.06–1.39), P=0.005] and random-effect models [OR=1.19, 95% CI (1.01–1.42), P=0.04]. Meta-regression analysis also supports the heterogeneity between the two subgroups (P=0.082). We also explored the role of this polymorphism on RA risk under other various interested genetic contrasts. These results further support that this polymorphism could not be a risk factor for Europeans. Interestingly, we find that in Asians the G allele has a greater tendency to cause RA in a recessive genetic model. However, sensitivity analysis showed that the combined result of Asian populations was unstable. In conclusion, our meta-analysis results suggest that CTLA-4 exon-1 +49G allele would not be a risk factor for RA in Europeans but might play a role in RA susceptibility for Asians.Shizhong Han and Yao Li have contributed equally to this paper.     

Association of <Emphasis Type="Italic">BLK</Emphasis> (rs13277113, rs2248932) polymorphism with systemic lupus erythematosus: a meta-analysis

The B-cell lymphocyte kinase (BLK) is a src-family protein tyrosine kinase specifically expressed in B-lineage cells that has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) and has been investigated in numerous ethnically diverse studies. However, genetic association studies that have examined the association between BLK gene variants and SLE have produced conflicting results. To shed further light on this issue, we performed a meta-analysis of the association between rs13277113, rs2248932 polymorphism and SLE in different ethnic groups. An updated literature-based meta-analysis of six original articles involving 20,271 control individuals and 11,796 subjects with SLE was conducted. Crude ORs with 95% CIs were used to assess the strength of association between rs13277113, rs2248932 polymorphism and SLE risk. Publication bias was estimated using Egger’s linear regression test. The authors assessed the evidence of genotypic association using STATA Version 10.0. The combined overall odds ratio, calculated for SLE and the risk A-allele of rs13277113 was 1.416 (95% CI: 1.358, 1.477). An odds ratio of 1.264 (95% CI: 1.208, 1.322) was found for the T-allele of rs2248932. Significant associations of rs13277113 and SLE were observed for dominant model (AA + AG vs. GG, OR: 1.518; 95% CI: 1.411, 1.632), and recessive model (AA vs. AG + GG, OR: 1.553; 95% CI: 1.461, 1.651); so were rs2248932 and SLE for dominant model (TT + TC vs. CC, OR: 1.342; 95% CI: 1.233, 1.460), and recessive model (TT vs. TC + CC, OR: 1.338; 95% CI: 1.257, 1.424). All of these were conducted in fixed effects model as heterogeneity was not detected. Tests for bias revealed no evidence of biases. On the assessment of available evidence, the authors concluded that moderate evidence exists for an association between the BLK rs13277113, rs2248932 variants and SLE. Therefore, further research is warranted on the role of BLK polymorphisms in the etiology of SLE.     

CDH1 promoter polymorphism and stomach cancer susceptibility

The relationship of stomach cancer susceptibility and the presence of E-cadherin (CDH1) promoter −160 C/A polymorphism had been reported with conflicting results. To further explore the association of this polymorphism with stomach cancer susceptibility, we performed an extensive search of relevant studies and carried out a meta-analysis to obtain a more precise estimate. A total of 16 studies including 2,611 cases and 3,788 controls were involved in this meta-analysis. When all studies involved, the meta-analysis results suggest no statistically significant association between CDH1 −160 C/A polymorphism and stomach cancer risk (CA vs. CC: OR = 1.01, 95% CI: 0.85–1.19; AA vs. CC: OR = 1.05, 95% CI: 0.75–1.46; dominant model: OR = 1.02, 95% CI: 0.86–1.20; recessive model: OR = 1.04, 95% CI: 0.76–1.41). When subgroup analyses were performed by ethnicity, the A-allele carriers conferred a decreased stomach cancer risk in Asians (AA vs. CC: OR = 0.67, 95% CI: 0.47–0.96; dominant model: OR = 0.85, 95% CI: 0.72–0.99), but no statistically significant association was found in Caucasians. In conclusion, this meta-analysis suggests that CDH1 −160 A-allele may play a protective role of stomach cancer development in Asians but not in Caucasians.     

Effect of LEPR Gln223Arg polymorphism on breast cancer risk in different ethnic populations: a meta-analysis

Leptin and leptin receptor have been implicated in processes leading to breast cancer initiation and progression. An A to G transition mutation in codon 223, in exon 6 of the leptin receptor gene (LEPR) can result in glutamine to arginine substitution (Gln223Arg). A variety of case–control studies have been published evaluating the association between LEPR Gln223Arg polymorphism and breast cancer. However, published studies have yielded contradictory conclusions. This meta-analysis enrolled eight studies to estimate the overall risk of LEPR Gln223Arg polymorphism associated with breast cancer. The pooled ORs were performed for codominant model (Arg/Arg versus Gln/Gln; Arg/Gln versus Gln/Gln), dominant model (Arg/Arg + Arg/Gln versus Gln/Gln), recessive model (Arg/Arg versus Arg/Gln + Gln/Gln). Overall significantly elevated breast cancer risk was found for recessive model (OR 1.32, 95% CI 1.03–1.69) and for genotype Arg/Gln versus Gln/Gln (OR 1.16, 95% CI 1.01–1.34). In the stratified analysis by ethnicity, significantly increased risks were also found among Africans for genotype Arg/Arg versus Gln/Gln: OR 1.86, 95% CI 1.28–2.71, Arg/Gln versus Gln/Gln: OR 1.48, 95% CI 1.10–1.99, dominant model: OR 1.60, 95% CI 1.21–2.11 and recessive model: OR 1.48, 95% CI 1.07–2.05; for Asians, Arg/Arg versus Gln/Gln: OR 6.79, 95% CI 3.42–13.47 and dominant model: OR 2.03, 95% CI 1.42–2.90. However, no significantly increased risk was found among Europeans for all genetic models. In conclusion, the LEPR 223Arg is a low-penetrant risk for developing breast cancer, especially for black African women.     

CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis

Several reports demonstrate association between variants of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune diseases. CTLA-4 may generate autoimmunity by immune dysregulation, making CTLA-4 an attractive candidate gene for systemic lupus erythematosus (SLE) susceptibility. Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 14 independent studies (to July 2004) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at four polymorphic sites found in exon-1 (at +49), the promoter region (at –318 and –1722), and the 3 untranslated region (3UTR) (dinucleotide repeat). We have evaluated both fixed and random effect models, depending on the presence of between-study heterogeneity. The data demonstrate that the exon-1 +49 polymorphism is significantly associated with SLE susceptibility. The overall risk, measured by odds ratio (OR), for exon-1 +49 GG genotype is 1.287 [95% confidence interval (CI)=1.031–1.562, P=0.011]. Stratification by ethnicity indicates the exon–1 +49 GG genotype is associated with SLE, at least in Asians (OR=1.293, 95% CI=1.031–1.620, P=0.026). European-derived populations have an effect of similar magnitude (OR=1.268, 95% CI=0.860–1.870, P=0.230), though not significant. Similar trends are found in allele-specific risk estimates and disease association. The OR for the exon-1 +49 risk allele (G) in Asians is 1.246 (95% CI=1.057–1.469, P=0.009), while Europeans have no evidence of allelic association (OR=0.978, 95% CI=0.833–1.148, P=0.780). In conclusion, this meta-analysis supports the CTLA-4 exon-1 +49 (A/G) polymorphism influencing the risk for developing SLE, especially in Asians.     

Association of angiotensin II type-1 receptor A1166C gene polymorphism with the susceptibility of end-stage renal disease

Abstract

Association between angiotensin II type-1 receptor (AT1R) A1166C gene polymorphism and end-stage renal disease (ESRD) risk is still controversial. This meta-analysis was performed to evaluate the association of AT1R A1166C gene polymorphism with ESRD susceptibility. The search was performed in the databases of PubMed, Embase and Cochrane Library as of 1 May 2012, and the eligible investigations were recruited for this meta-analysis. Nineteen literatures were identified for the analysis of association between AT1R A1166C gene polymorphism and ESRD susceptibility. There was no association between AT1R A1166C gene polymorphism and ESRD susceptibility for overall populations, Caucasians, Asians and Turkish population. Interestingly, CC genotype was associated with a higher risk of ESRD in Africans (OR?=?3.36, 95% CI: 1.42–7.99, p?=?0.006). However, C allele and AA genotype were not associated with the ESRD risk in African population. In conclusion, CC genotype might be a risk factor for the ESRD susceptibility in African population. However, more case-control association investigations on larger, stratified populations are required in the future.     

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

The aim of this study was to determine whether the interleukin-10 (IL-10) polymorphisms confer susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the IL-10 −1082 G/A, −592 C/A, −892 C/T and IL-10.R polymorphisms and RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 16 studies (19 comparisons) involving 2647 RA patients and 3383 controls were considered in the meta-analysis. Meta-analysis of the IL-10 −1082 G/A polymorphism showed no association with RA in the study subjects, or in European or Asian subjects. However, meta-analysis of the −1082 G allele in 4 studies in Hardy–Weinberg equilibrium showed a significant association with RA (OR = 1.217, 95% CI = 1.027–1.442, P = 0.0236). In contrast, meta-analysis of the C allele, the CC genotype, and of the CC versus the AA genotype of the IL-10 −592 C/A polymorphism showed significant associations with RA. The overall ORs of the associations between the C allele and RA were 0.684 and 0.758 (95% CI = 0.494–0.946, P = 0.022; 95% CI = 0.475–1.210, P = 0.045) in all study subjects and Asians. Meta-analysis of the CC + CT versus TT genotype and of the CC versus TT genotype of the IL-10 −892 C/T polymorphism revealed significant associations with RA. The overall OR of the association between the C allele carrier and RA was 0.552 (95% CI = 0.375–0.812, P = 0.003). No association was found between the IL10.R2 alleles and RA. This meta-analysis suggests that the IL-10 −592 C/A polymorphism confers susceptibility to RA in Asians and that the IL-10 −1082 G/A and −892 C/T polymorphisms are associated with RA susceptibility. These findings suggest the IL-10 genes confer susceptibility to RA.     

Association between MTHFR C677T polymorphism and osteonecrosis of the femoral head: a meta-analysis

The results of studies on association between the C677T polymorphism of the 5,10-methylene-tetrahydrofolate reductase (MTHFR) gene and osteonecrosis of the femoral head (ONFH) are controversial. To derive a more precise estimation of the relationship between the MTHFR C677T polymorphism and ONFH, a meta-analysis was performed. Eight studies on MTHFR C677T association with ONFH were searched up to April 2011, and the genotype frequencies in control group were consistent with Hardy–Weinberg equilibrium. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Publication bias was tested by funnel plot, Egger’s regression test, and heterogeneity was assessed. Eight studies containing 778 cases and 1,162 controls were included. Heterogeneity was observed (χ ² = 18.58, P = 0.01). Under the random effects model, the common OR was 1.38 (95% CI: 0.92–2.08; P = 0.12). In the subgroup meta-analysis, there was an association between MTHFR C677T polymorphism and ONFH in non-Asian population for CT + TT vs. CC (OR = 1.72; 95% CI: 1.21–2.43; P = 0.002; I ²  = 37.9%, P = 0.17), but not for Asian population (OR = 0.88; 95% CI: 0.66–1.66; P = 0.35; I ²  = 45.4%, P = 0.16). There was heterogeneity between studies and no clear evidence of an association on a worldwide population. When stratifying for the race, this meta-analysis did not provide an evidence of confirming association between MTHFR C677T polymorphism and ONFH. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of MTHFR C677T polymorphism with ONFH susceptibility.     

Transforming growth factor-β1 gene +869T/C,but not +915G/C polymorphism is associated with essential hypertension in a Chinese patient cohort

Many studies have suggested that transforming growth factor-β1 (TGF-β1) gene might be involved in the development of hypertension. However, results have been inconsistent. In this study, the authors performed a meta-analysis to investigate the associations of +869T/C and +915G/C polymorphisms in TGF-β1 gene with hypertension risk in Chinese. Published literature from PubMed, EMBASE, CNKI, CBM, and Wanfang Data were searched. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed or random-effects model. Nine studies (1,995 cases/1,840 controls) for +869T/C polymorphism and seven studies (1,547 cases/1,577 controls) for +915G/C polymorphism were included in the meta-analysis. The overall result showed that there was a statistically significant association between +869T/C polymorphism and hypertension risk (CC vs. TT: OR = 1.80, 95% CI 1.34–2.44). Similar results were found among two geographic locations and two subgroups with different sample size. However, no significant association was found for +915G/C polymorphism with the risk of hypertension (CC vs. GG: OR = 1.66, 95% CI 0.74–3.74). The meta-analysis indicated the significant association of +869T/C, but not +915G/C polymorphism with hypertension susceptibility. However, given the limited sample size, the associations warrant further investigation.     

Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis

The aim of this study was to determine whether the vitamin D receptor (VDR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). A meta-analysis was conducted on the associations between the BsmI, TaqI, FokI, and ApaI polymorphisms of VDR and RA or SLE using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of ten studies, six RA and four SLE studies, were considered in the meta-analysis. Meta-analysis of the VDR BsmI and TaqI polymorphisms showed no association between RA in all subjects, or in European or Asian subjects. In contrast, meta-analysis of the F allele, the FF genotype, and the FF vs. the ff genotype of the FokI polymorphism showed significant associations with RA in Europeans. The overall OR of the association between the F allele and RA was 1.502 (95% CI = 1.158–1.949, P = 0.002). Meta-analysis of the B allele, BB + Bb genotype, and BB genotype (additive model) of the BsmI polymorphism showed significant associations with SLE and LN in Asians. The overall ORs of the associations between the B allele and SLE and LN were 3.584 (95% CI = 1.407–9.130, P = 0.007) and 3.652 (95% CI = 1.347–9.902, P = 0.011). This meta-analysis demonstrates that the VDR FokI polymorphism may confer susceptibility to RA in Europeans. Furthermore, associations were found between the VDR BsmI polymorphism and susceptibilities to SLE and LN in Asians.     

Meta-analysis on the association of nucleotide excision repair gene XPD A751C variant and cancer susceptibility among Indian population

Polymorphism A751C (A>C) in XPD gene has shown susceptibility to many cancers in Indian population; however the results of these studies are inconclusive. Thus, we performed this meta-analysis to estimate the association between XPD A751C polymorphism and overall cancer susceptibility. We quantitavely synthesized all published studies of the association between XPD A751C polymorphism and cancer risk. Pooled odds ratios (ORs) and 95 % CI were estimated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of thirteen studies including 3,599 controls and 3,087 cancer cases were identified and analyzed. Overall significant results were observed for C allele carrier (C vs. A: p = 0.001; OR 1.372, 95 % CI 1.172–1.605) variant homozygous (CC vs. AA: p = 0.001; OR 1.691, 95 % CI 1.280–2.233) and heterozygous (AC vs. AA: p = 0.001; OR 1.453, 95 % CI 1.215–1.737) genotypes. Similarly dominant (CC+AC vs. AA: p = 0.001; OR 1.512, 95 % CI 1.244–1.839) and recessive (CC vs. AA+AC: p = 0.001; OR 1.429, 95 % CI 1.151–1.774) genetic models also demonstrated risk of developing cancer. This meta-analysis suggested that XPD A751C polymorphism likely contribute to cancer susceptibility in Indian population. Further studies about gene–gene and gene–environment interactions are required.     

Survivin promoter ?31G/C (rs9904341) polymorphism and cancer susceptibility: a meta-analysis

This study aimed to perform a meta-analysis to assess the association of survivin −31 G/C promoter polymorphism and cancer risk. Thirteen case–control studies identified through PubMed and published between 2007 and 2011 with a total of 3329 cancer cases and 3979 controls were included in this meta-analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Overall, the pooled analysis showed that survivin −31C allele was associated with 1.27 fold increased risk of cancer compared with the −31G allele (95% CI = 1.091–1.479; random model). Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that survivin −31G/C polymorphism was not associated with risk of gastric cancer [OR = 2.879; 95% CI = 0.553–15.004) for CC vs.GG] and esophageal cancer [OR = 1.352; 95% CI = 0.494–3.699) for CC vs.GG]. Stratification on the basis of ethnicity showed that the risk due to −31C allele was significant only in Asian population [OR = 1.894; 95% CI = 1.206–2.974 for CC vs.GG]. The present meta-analysis suggests an important role of survivin −31 G/C polymorphism with cancer risk especially in Asian population. However, further studies with larger sample size are required to draw more comprehensive conclusions and provide more precise evidence in individual cancers.     

Association between the G-protein β3 subunit C825T polymorphism with essential hypertension: a meta-analysis in Han Chinese population

We aimed to evaluate the contribution of the G-protein β3 subunit C825T (GNB3-C825T) polymorphism to essential hypertension (EH) in Han Chinese population by performing meta-analysis. A meta-analysis was performed in 12 case-control genetic association studies including 3,020 hypertension patients and 2,790 controls from MEDLINE (PubMed) and the China National Knowledge Infrastructure platforms. The STATA 10.0 software was used in analysis. Overall, there was no significant association between the GNB3-C825T polymorphism and EH in neither additive [TT vs. CC: OR (95 % CI) = 1.11 (0.74-1.69), P = 0.61; TC vs. CC: OR (95 % CI) = 1.08 (0.89-1.31), P = 0.42], nor dominant [TT + TC vs. CC: OR (95 % CI) = 1.11 (0.86-1.42), P = 0.43] and nor recessive [TT vs. TC + CC: OR (95 % CI) = 1.04 (0.75-1.44), P = 0.81] genetic models. Although further subgroup analysis found statistically significant results [T vs. C: OR (95 % CI) = 1.50 (1.05-2.15), P = 0.03] in the southern population, but after exclusion one particular study, the significant association was disappeared. No significant result was found in the northern Han Chinese population. There was no significant association identified between GNB3-C825T polymorphism and EH in Han Chinese population. Further larger sample and well-designed studies are needed to assess the genetic association particularly in the southern Han Chinese population.     

<Emphasis Type="Italic">Complement factor H</Emphasis> Y402H gene polymorphism and coronary heart disease susceptibility: a meta-analysis

The complement factor H (CFH) Y402H (T1277C) gene polymorphism has been reported to be associated with coronary heart disease (CHD), but results were conflicting. To evaluate the role of the variant in CHD, we performed meta-analyses of all available data. Both electronic and manual searches were performed, all relevant studies were identified. ORs with 95% confidential intervals (CI) under codominant (CC versus TT, TC versus TT), dominant (CC + TC versus TT) and recessive (CC versus TT + TC) models were calculated. Publication bias was addressed. Ten studies including 11 cohorts comprising of 29,764 participants were included. No association between the CFH T1227C polymorphism and CHD could be found. (For overall analysis: dominant model, OR = 1.04, 95%CI: 0.97–1.11; recessive model, OR = 1.04, 95%CI: 0.97–1.11; for Caucasian subgroup: OR = 1.08 95%CI: 0.92–1.27; recessive model, OR = 1.03, 95%CI: 0.96–1.11). Two studies reported positive results in separate population (Caucasian study: recessive model, OR = 0.51, 95%CI: 0.30–0.86; Asians study: dominant model, OR = 2.37, 95%CI: 1.13–4.96). Current evidence do not support the association between the CFH T1277C polymorphism and CHD risk among common population. The association, which could be influenced by CHD onset age, CHD risk factors status and genetics backgrounds, might be significant in some population. More studies on different CHD onset ages and risk factor status should be encouraged.     

Contribution of STAT4 gene single-nucleotide polymorphism to systemic lupus erythematosus in the Polish population

The STAT4 has been found to be a susceptible gene in the development of systemic lupus erythematosus (SLE) in various populations. There are evident population differences in the context of clinical manifestations of SLE, therefore we investigated the prevalence of the STAT4 G > C (rs7582694) polymorphism in patients with SLE (n = 253) and controls (n = 521) in a sample of the Polish population. We found that patients with the STAT4 C/G and CC genotypes exhibited a 1.583-fold increased risk of SLE incidence (95 % CI = 1.168-2.145, p = 0.003), with OR for the C/C versus C/G and G/G genotypes was 1.967 (95 % CI = 1.152-3.358, p = 0.0119). The OR for the STAT4 C allele frequency showed a 1.539-fold increased risk of SLE (95 % CI = 1.209-1.959, p = 0.0004). We also observed an increased frequency of STAT4 C/C and C/G genotypes in SLE patients with renal symptoms OR = 2.259 (1.365-3.738, p = 0.0014), (p (corr) = 0.0238) and in SLE patients with neurologic manifestations OR = 2.867 (1.467-5.604, p = 0.0016), (p (corr) = 0.0272). Moreover, we found a contribution of STAT4 C/C and C/G genotypes to the presence of the anti-snRNP Ab OR = 3.237 (1.667-6.288, p = 0.0003), (p (corr) = 0.0051) and the presence of the anti-Scl-70 Ab OR = 2.665 (1.380-5.147, p = 0.0028), (p (corr) = 0.0476). Our studies confirmed an association of the STAT4 C (rs7582694) variant with the development of SLE and occurrence of some clinical manifestations of the disease.     

Association between two genetic polymorphisms of the renin-angiotensin-aldosterone system and diabetic nephropathy: a meta-analysis

The widely studied candidate genes of the renin-angiotensin-aldosterone system, angiotensinogen (AGT), and angiotensin II receptor type 1 (AGTR1), are implicated in the development of diabetic nephropathy (DN). A number of studies have evaluated the association between the functional polymorphisms, AGT M235T and AGTR1 A1166C, and DN risk with conflicting results. The present meta-analysis was performed to estimate the overall risk of these polymorphisms associated with DN on 4,377 DN cases and 4,905 controls from 34 published case–control studies by searching electronic databases and reference lists of relevant articles. We examined the association between each polymorphism and the risk of DN by odds ratio (OR) with 95% confidence intervals (95% CI) and calculated the ORs for different genetic model. In addition, stratification analysis by ethnicity and diabetes mellitus (DM) type was conducted. In this meta-analysis, we failed to find any significant main effects in both overall analysis and stratified analysis for the AGT M235T. However, the overall analysis detected a significant association between the AGTR1 A1166C and the risk of DN for the CC compared with the AA and dominant genetic model (CC vs. AA: OR = 2.10, 95% CI: 1.00–4.44; dominant model: OR = 2.11, 95% CI: 1.06–4.23). In subgroup analysis, only patients with T2DM showed significant association for CC vs. AA model and dominant model (CC vs. AA: OR = 3.31, 95% CI: 1.21–9.08; dominant model: OR = 3.50, 95% CI: 1.41–8.69). This study suggests that the AGTR1 A1166C polymorphism may contribute to DN development, particularly in T2DM patients.     

Lack of association between <Emphasis Type="Italic">MDR1</Emphasis> C3435T polymorphism and chemotherapy response in advanced breast cancer patients: evidence from current studies

The transmembrane transport of anticancer drugs is mainly regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 gene (MDR1). Since there were controversies regarding the association between MDR1 C3435T polymorphism and response to chemotherapy among patients with advanced breast cancer, a meta-analysis of the link was conducted. A total of 7 studies consist of 464 advanced breast cancer patients relating MDR1 C3435T polymorphism to the response of chemotherapy were included in this meta-analysis. The main analysis revealed a lack of association between the MDR1 C3435T and response to chemotherapy, with odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) of 1.37 (95% CI: 0.78–2.40), 1.17 (95% CI: 0.69–2.01), 1.18 (95% CI: 0.76–1.84) and 1.61 (95% CI: 0.70–3.68) for homozygous comparison, heterozygous comparison, dominant model and recessive model, respectively. The subgroup analysis by ethnicity did not change the pattern of results, with ORs of 0.99 (95% CI: 0.11–9.07), 0.68 (95% CI: 0.29–1.60), 0.81 (95% CI: 0.36–1.85) and 1.51 (95% CI: 0.77–2.96), in homozygous comparison, heterozygous comparison, dominant model and recessive model, respectively in Caucasian, and 1.50 (95% CI: 0.75–3.03), 1.72 (95% CI: 0.85–3.47), 1.59 (95% CI: 0.90–2.80) and 2.29 (95% CI: 0.51–10.35), respectively in Asian. The available evidence indicates that MDR1 C3435T polymorphism cannot be considered as a reliable predictor of response to chemotherapy in patients with advanced breast cancer.     

A meta-analysis on the association between three promoter variants of TNF-α and Crohn’s disease

Tumor necrosis factor-alpha (TNF-α) has been regarded as a candidate gene for Crohn’s disease (CD) based on its inflammatory function in immune reaction and the clinical effectiveness of anti-TNF-α therapy. However, studies to date have reported inconsistent findings for the association between TNF-α and CD. The PubMed, EMBASE, and Medline databases were systematically reviewed from all English language publications up to April, 2011. A total of twenty-nine studies concerning the association between CD and the TNF-α promoter polymorphisms of −308G/A, −857C/T and −238G/A were identified, among of them only twenty-three studies match the inclusion criteria (including 3,843 cases and 6,260 controls) and were selected for the statistical test. We found that neither the G allele of −308G/A (OR 1.02, 95% CI 0.87–1.19, P = 0.84), C allele of −857C/T (OR 0.97, 95% CI 0.86–1.09, P = 0.57) and G allele of −238G/A (OR 0.91, 95% CI 0.70–1.18, P = 0.48), and nor their GG (OR 1.05, 95% CI 0.88–1.25, P = 0.59), CC (OR 0.98, 95% CI 0.86–1.12, P = 0.76) and GG (OR 0.92, 95% CI 0.70–1.21, P = 0.55) genotypes were associated with CD susceptibility, respectively. Our meta-analysis demonstrates that three promoter polymorphisms of TNF-α above may not confer susceptibility to CD.