Genetic polymorphism of apolipoprotein A5 gene and susceptibility to type 2 diabetes mellitus: a meta-analysis of 15,137 subjects.

BACKGROUND: Several studies have investigated whether the polymorphism in the apolipoprotein A5 (APOA5) is associated with type 2 diabetes mellitus (T2DM) risk. However, those studies have produced inconsistent results. The purpose of this study was to investigate whether the APOA5 -1131T/C polymorphism (rs662799) confers significant susceptibility to T2DM using a meta-analysis. METHODS: PubMed, Embase, Web of Science, Cochrane database, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. RESULTS: A total of 19 studies included 4,767 T2DM cases and 10,370 controls (four studies involving 555 T2DM cases and 2958 controls were performed among Europeans and 15 studies involving 4212 T2DM cases and 7412 controls were performed among Asians) were combined showing significant association between the APOA5 -1131T/C polymorphism and T2DM risk (for C allele vs. T allele: OR = 1.28, 95% CI = 1.17-1.40, p<0.00001; for C/C vs. T/T: OR = 1.57, 95% CI = 1.35-1.83, p<0.00001; for C/C vs. T/C+T/T: OR = 1.36, 95% CI = 1.18-1.57, p<0.0001; for C/C+T/C vs. T/T: OR = 1.32, 95% CI = 1.16-1.51, p<0.0001). In the subgroup analysis by ethnicity, significant association was also found among Asians (for C allele vs. T allele: OR = 1.31, 95% CI = 1.22-1.40, p<0.00001; for C/C vs. T/T: OR = 1.61, 95% CI = 1.38-1.88, p<0.00001; for C/C vs. T/C+T/T: OR = 1.39, 95% CI = 1.20-1.61, p<0.0001; for C/C+T/C vs. T/T: OR = 1.42, 95% CI = 1.25-1.62, p<0.00001). However, no significant association was found between the APOA5 -1131T/C polymorphism and T2DM risk among Europeans. CONCLUSIONS: The present meta-analysis suggests that the APOA5 -1131T/C polymorphism is associated with an increased T2DM risk in Asian population.

Influence of apolipoprotein E gene polymorphism on development of type 2 diabetes mellitus in Chinese Han population: a meta-analysis of 29 studies.

OBJECTIVES: Published data regarding the association between apolipoprotein E (ApoE) gene polymorphism and type 2 diabetes mellitus (T2DM) risk in Chinese Han population were inconclusive. To derive a more precise estimation of the relationship between this variant and T2DM risk in Chinese Han population, we performed this meta-analysis. DESIGN AND METHODS: A computerized literature search was conducted to identify the relevant studies from PubMed, EMbase, Web of Science, CBMdisc, CNKI, and Google Scholar. Additionally, hand searching of the references of identified articles was performed. All the statistical tests were performed using Stata 11.0. RESULTS: A total of 29 articles with 4615 T2DM cases and 2867 controls were included in the present meta-analysis. The results showed evidence for significant association between ApoE gene polymorphism and T2DM risk (for ε2/ε3 vs. ε3/ε3: OR=1.37, 95% CI=1.12-1.68, P<0.01; for ε3/ε4 vs. ε3/ε3: OR=1.53, 95% CI=1.23-1.91, P<0.01; for ε4/ε4 vs. ε3/ε3: OR=1.86, 95% CI=1.22-2.84, P<0.01; for ε2 allele vs. ε3 allele: OR=1.28, 95% CI=1.08-1.52, P=0.01; for ε4 allele vs. ε3 allele: OR=1.43, 95% CI=1.22-1.68, P<0.01). In addition, significant association was also found between ApoE gene polymorphism and diabetic nephropathy (DN) risk. CONCLUSIONS: The results of this meta-analysis suggest that the ApoE ε2 and ε4 alleles may be associated with increased risks of T2DM and DN in Chinese Han population. Additional well-designed genome-wide association studies are required to confirm these results.

Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Chinese population: evidence from a meta-analysis of 40 studies.

BACKGROUND: Epidemiological studies have evaluated the association between apolipoprotein E (ApoE) gene polymorphism and coronary artery disease (CAD) risk which developed inconsistent conclusions. To derive a more precise estimation of the relationship in Chinese population, we performed this meta-analysis. METHODS: Databases, including PubMed, EMbase, Web of Science, CBMdisc and CNKI, were searched to get the genetic association studies. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Review Manager 5.1.2 and Stata 11.0. RESULTS: We identified a total of 40 studies, including 4,564 CAD cases and 3,985 controls. The results showed evidence for significant association between ApoE ε4 allele and CAD risk (for ε2/ε4 vs. ε3/ε3: OR = 1.86, 95% CI = 1.42-2.43, p<0.00001; for ε3/ε4 vs. ε3/ε3: OR = 2.34, 95% CI = 2.07-2.65, p<0.00001; for ε4/ε4 vs. ε3/ε3: OR = 2.89, 95% CI = 1.87-4.47, p<0.00001; for ε4 allele vs. ε3 allele: OR = 2.11, 95% CI = 1.91-2.35, p<0.00001). CONCLUSIONS: The present meta-analysis suggests an association between ApoE ε4 allele and increased risk of CAD in Chinese population. 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.

The lack of association between interleukin-6 gene -174 G/C polymorphism and the risk of type 1 diabetes mellitus: a meta-analysis of 18,152 subjects.

Epidemiological studies have evaluated the association between interleukin-6 (IL-6) gene -174 G/C polymorphism and type 1 diabetes mellitus (T1DM) risk, but results of different studies have been inconsistent. The present meta-analysis was therefore designed to clarify these controversies. PubMed, Embase and Web of Science were searched from the first available year to March 25, 2012, as well as hand searching of the references of identified articles were performed. All studies investigating the association between IL-6 gene -174 G/C polymorphism and T1DM risk were included. Data analyses were carried out by Review Manager 5.1.2 and Stata 11.0. Seven studies were included in the final meta-analysis, covering a total of 9697 T1DM cases and 8455 controls. The results showed no evidence for significant association between IL-6 gene -174 G/C polymorphism and T1DM risk (for C/C+C/G vs. G/G: OR=1.30, 95% CI=0.84-2.00, p=0.24; for C/C vs. C/G+G/G: OR=1.10, 95% CI=0.75-1.60, p=0.63; for C/C vs. G/G: OR=1.34, 95% CI=0.75-2.42, p=0.33; for C allele vs. G allele: OR=1.16, 95% CI=0.88-1.53, p=0.30). In addition, the similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta-analysis suggests that IL-6 gene -174 G/C polymorphism is not associated with T1DM risk. 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.

Associations between interleukin-6 gene -174 C/G and -572 C/G polymorphisms and the risk of gastric cancer: a meta-analysis.

BACKGROUND AND OBJECTIVES: Epidemiological studies have evaluated the associations between interleukin-6 (IL-6) gene -174 C/G (rs1800795) and -572 C/G (rs1800796) polymorphisms and gastric cancer (GC) risk, but results and conclusions remain controversial. In order to derive a more precise estimation of the associations, we performed this meta-analysis. METHODS: A meta-analysis was conducted to estimate the associations between IL-6 gene -174 C/G and -572 C/G polymorphisms and GC risk. RESULTS: Nine articles involving 13 studies were included in the final meta-analysis, covering a total of 1,581 GC cases and 2,563 controls. For IL-6 gene -174 C/G polymorphism, nine studies were combined showing no evidence for associations between IL-6 gene -174 C/G polymorphism and GC risk. For IL-6 gene -572 C/G polymorphism, four studies were combined. There was also lack of evidence for significant association between IL-6 gene -572 C/G polymorphism and GC risk. In addition, the similar results were obtained in the subgroup analyses and cumulative meta-analysis. CONCLUSIONS: The present meta-analysis suggests that IL-6 gene -174 C/G and -572 C/G polymorphisms are not associated with GC risk. However, due to the small subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.

Association between interleukin-6 gene -174 G/C polymorphism and the risk of coronary heart disease: a meta-analysis of 20 studies including 9619 cases and 10,919 controls.

Interleukin-6 (IL-6) gene -174 G/C polymorphism has been reported to be associated with coronary heart disease (CHD), but the results remain inconclusive. The present meta-analysis was therefore designed to clarify these controversies. This meta-analysis was performed by searching PubMed, Embase and Web of Science databases. A total of 20 studies including 9619 CHD cases and 10,919 controls were combined showing no evidence of association between IL-6 gene -174 G/C polymorphism and CHD risk (for C/C+C/G vs. G/G: OR=1.10, 95% CI=0.99-1.22, p=0.07; for C/C vs. C/G+G/G: OR=1.08, 95% CI=0.93-1.24, p=0.33; for C/C vs. G/G: OR=1.16, 95% CI=0.97-1.39, p=0.11; for C allele vs. G allele: OR=1.10, 95% CI=1.00-1.21, p=0.06). Moreover, we also did not find significant association between IL-6 gene -174 G/C polymorphism and myocardial infarction (MI) risk. However, in the subgroup analysis by ethnicity, significant association was found among Asians (for C/C+C/G vs. G/G: OR=1.35, 95% CI=1.05-1.63, p=0.02). In summary, the present meta-analysis suggests that IL-6 gene -174 G/C polymorphism is associated with increased CHD risk among Asians. However, due to the small subjects included in the subgroup analysis of Asians, the results should be interpreted with caution.

Association between tumor necrosis factor-alpha gene -308A/G polymorphism and the risk of acute pancreatitis: a meta-analysis.

BACKGROUND: Epidemiologic studies have evaluated the association between tumor necrosis factor-alpha (TNF-α) gene -308A/G polymorphism and the risk of acute pancreatitis (AP), but the results are inconsistent. In order to derive a more precise estimation of the associations, a meta-analysis was performed. MATERIALS AND METHODS: Systematic searches of electronic databases PubMed, Embase, and Web of Science, as well as hand searching of the references of identified articles, were performed. All case-control studies investigating the association between TNF-α gene -308A/G polymorphism and AP risk were included. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs). Publication bias was analyzed by Begg's funnel plot and Egger's regression test. RESULTS: The initial search revealed 818 potentially eligible studies. Having read the title, abstract, or full text, we included six relevant studies in the final meta-analysis, which contained 1,006 AP cases and 782 controls. Overall, no significant association was found between TNF-α gene -308A/G polymorphism and AP risk when all studies were pooled into the meta-analysis (for A/A+A/G versus G/G: OR = 1.03, 95% CI = 0.83-1.28, P = 0.79; for A/A versus A/G+G/G: OR = 0.97, 95% CI = 0.65-1.45, P = 0.87; for A/A versus G/G: OR = 1.23, 95% CI = 0.79-1.91, P = 0.37; for A allele versus G allele: OR = 0.99, 95% CI = 0.83-1.18, P = 0.90). In addition, the similar results were obtained in the subgroup analysis based on the ethnicity and subtype of AP. CONCLUSIONS: The present meta-analysis reveals that the TNF-α gene -308A/G polymorphism is not associated with AP risk. However, due to the small number of subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.