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A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk.

ABSTRACT: Leptin receptor (LEPR) plays a pivotal role in the control of body weight, energy metabolism, and insulin sensitivity. Various genetic association studies were performed to evaluate associations of LEPR genetic variants with type 2 diabetes (T2D) susceptibility.A comprehensive search was conducted to identify all eligible case-control studies for examining the associations of LEPR single nucleotide polymorphisms (SNPs) Q223R (rs1137101) and K109R (rs1137100) with T2D risk. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were used to measure the magnitudes of association.For Q223R, 13 studies (11 articles) consisting of a total of 4030 cases and 2844 controls, and for K109R 7 studies (7 articles) consisting of 3319 cases and 2465 controls were available. Under an allele model, Q223R was not significantly associated with T2D risk (OR = 1.09, 95% CI: 0.80-1.48, P-value = 0.5989), which was consistent with results obtained under four genotypic models (ranges: ORs 1.08-1.20, 95% CIs: 0.58-2.02 to 0.64-2.26; P-values, 0.3650-0.8177, which all exceeded multiplicity-adjusted ? = 0.05/5 = 0.01). In addition, no significant association was found between K109R and T2D risk based on either an allele model (OR = 0.93, 95% CI: 0.85-1.03, P-value = 0.1868) or four genotypic models (ranges: ORs 0.81-0.99, 95% CIs: 0.67-0.86 to 0.97-1.26, P-values, 0.0207-0.8804 which all exceeded multiplicity-adjusted ? of 0.01). The magnitudes of association for these two SNPs were not dramatically changed in subgroup analyses by ethnicity or sensitivity analyses. Funnel plot inspections as well as Begg and Mazumdar adjusted rank correlation test and Egger linear regression test did not reveal significant publication biases in main and subgroup analyses. Bioinformatics analysis predicted that both missense SNPs were functionally neutral and benign.The present meta-analysis did not detect significant genetic associations between LEPR Q223R and K109R polymorphisms and T2D risk.

SUBMITTER: Yang Y

PROVIDER: S-EPMC5749718 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk.

Yang Yunzhong Y Niu Tianhua T

PloS one 20180102 1

<h4>Background</h4>Leptin receptor (LEPR) plays a pivotal role in the control of body weight, energy metabolism, and insulin sensitivity. Various genetic association studies were performed to evaluate associations of LEPR genetic variants with type 2 diabetes (T2D) susceptibility.<h4>Methods</h4>A comprehensive search was conducted to identify all eligible case-control studies for examining the associations of LEPR single nucleotide polymorphisms (SNPs) Q223R (rs1137101) and K109R (rs1137100) wi ...[more]

PMID: 29293570

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Project description:BACKGROUND: Associations between transcription factor 7-like 2 (TCF7L2) polymorphisms and type 2 diabetes mellitus (T2DM) have been evaluated extensively in multiple ethnic groups. TCF7L2 has emerged as the strongest T2DM susceptibility gene in Europeans, but the findings have been inconsistent in the Chinese population. The purpose of this meta-analysis was to evaluate the associations between TCF7L2 single nucleotide polymorphisms (SNPs) and T2DM risk in the Chinese population. METHODS: We performed searches in the PubMed, EMBASE, Cochrane, and Chinese databases (CNKI, CQVIP and Wanfang databases) for literature published from January 2007 to February 2012. We reviewed all relevant articles on TCF7L2 polymorphisms and susceptibility to T2DM in the Chinese population written in English and Chinese. Two reviewers extracted data independently using a standardized protocol, and any discrepancies were adjudicated by a third reviewer. Fixed-effects and random-effects meta-analyses were performed to pool the odds ratios (ORs). Publication bias and heterogeneity were examined. RESULTS: A total of 21 articles were confirmed to be eligible for and included in this meta-analysis: 7 (with 3942 cases and 3502 controls) concerning rs11196218 (IVS-/+4G>A), 8 (with 3377 cases and 2975 controls) concerning rs290487 (IVS3-/+C>T), and 14 (with 7902 cases and 7436 controls) concerning rs7903146 (IVS3-/+C>T). Overall, the results showed a significant association between rs7903146 and T2DM risk. The pooled ORs were 1.54 for the comparison of T and C alleles (95% CI [confidence interval]: 1.37-1.74, p = 1.47 × 10-12, I2 = 25.20%) and 1.56 for TC heterozygotes and CC homozygotes (95% CI : 1.38-1.76, p = 8.25 × 10-9, I2 = 21.00%). The rs11196218(IVS4G>A) and rs290487 (IVS3C>T) SNPs were not associated with T2DM risk. CONCLUSIONS: The rs7903146 SNP of the TCF7L2 gene is associated with increased susceptibility to T2DM in the Chinese population as a whole as well as northern Chinese and southern Chinese as subgroups.

Project description:BackgroundPrevious studies have examined the role of the KQT-like subfamily Q member1 (KCNQ1) gene polymorphisms on the risk of type 2 diabetes mellitus (T2DM), but the findings are inconclusive.ObjectiveTo examine the association between the KCNQ1 gene polymorphisms and the risk of T2DM using an updated meta-analysis with an almost tripled number of studies.MethodsFive electronic databases, such as PubMed and Embase, were searched thoroughly for relevant studies on the associations between seven most studied KCNQ1 gene polymorphisms, including rs2237892, rs2237897, rs2237895, rs2283228, rs231362, rs151290, and rs2074196, and T2DM risk up to September 14, 2019. The summary odds ratios (ORs) with their 95% confidence intervals (CIs) were applied to assess the strength of associations in the random-effects models. We used the trial sequential analysis (TSA) to measure the robustness of the evidence.Results49 publications including 55 case-control studies (68,378 cases and 66,673 controls) were finally enrolled. In overall analyses, generally, increased T2DM risk was detected for rs2237892, rs2237895, rs2283228, rs151290, and rs2074196, but not for rs231362 under all genetic models. The ORs and 95% CIs for allelic comparison were 1.23 (1.14-1.33) for rs2237892, 1.21 (1.16-1.27) for rs2237895, 1.27 (1.11-1.46) for rs2237897, 1.25 (1.09-1.42) for rs2283228, 1.14 (1.03-1.27) for rs151290, 1.31 (1.23-1.39) for rs2074196, and 1.16 (0.83, 1.61) for rs231362. Stratified analyses showed that associations for rs2237892, rs2237895, rs2283228, and rs151290 were more evident among Asians than Caucasians. TSA demonstrated that the evidence was sufficient for all polymorphisms in this study. The genotypes of the three SNPs (rs2237892, rs2283228, and rs231362) were significantly correlated with altered KCNQ1 gene expression.ConclusionThis meta-analysis suggested that KCNQ1 gene polymorphisms (rs2237892, rs2283228, rs2237895, rs151290, and rs2074196) might be the susceptible factors for T2DM, especially among Asian population.

Project description:BackgroundGrowing body of evidence suggest the association between SNP - 11377 C > G and SNP + 276 G > T polymorphisms of adiponectin gene with type 2 diabetes (T2D). However, these findings have not been conclusive and consistent. The present study quantitatively evaluates the data on the association between DIPOQ - 11377C/G, and + 276G/T polymorphisms and risk of T2D through a meta-analysis.MethodsA systematic search was performed in the PubMed, Web of science, Scopus and Cochrane library databases to extract published studies according to the inclusion criteria. Among the 741 studies, 391 of them were screened as full text and 31 studies were finally included in the meta-analysis. Analysis of data was performed using random-effects model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to analyze the strength of association. Subgroup and meta-regression analyses were performed to identify the potential source of heterogeneity.ResultsThe pooled analysis showed that there was no statistically significant association between genotypes of CC (OR = 0.76, 95% CI: 0.53-1.09, P = 0.14), CG (OR = 0.93, 95% CI: 0.72-1.20, P = 0.58) and GG (OR = 1, 95% CI: 0.80-1.26, P = 0.94) ADIPO - 11377 polymorphism with increased risk of T2D. In addition, the results revealed a trend toward an increased risk of T2D for the SNP + 276 TT genotype (OR = 0.87, 95% CI: 0.77-0.98, P = 0.026) as compared with the GT and GG genotypes. Subgroup analysis by ethnicity indicated significant association between the TT genotype of the SNP + 276 and increased risk of T2D among Europeans. Met-regression demonstrated significant association between the GT genotype of + 276 polymorphism with risk of T2D in male individuals (slope: 0.0006; 95% CI: 0.0002-0.0009; P < 0.001).ConclusionsCollectively, our findings demonstrated a positive association between ADIPOQ + 276 G > T polymorphism with increased risk of T2D in male individuals with European ethnicity.

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A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk.

Publications

A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk.

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