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Variations in the Obesity Gene "LEPR" Contribute to Risk of Type 2 Diabetes Mellitus: Evidence from a Meta-Analysis.

ABSTRACT: Leptin is a hormone protein regulating food intake and energy expenditure. A number of studies have evaluated the genetic effect of leptin (LEP) and leptin receptor (LEPR) genes on T2DM. This study aimed to investigate the association between these gene polymorphisms and T2DM by a systematic review and meta-analysis. Published studies were identified through extensive search in PubMed and EMBASE. A total of 5143 T2DM cases and 5021 controls from 14 articles were included in this study. Five functional variants in LEPR were well evaluated. Meta-analysis showed that rs1137101 (p.R223Q) was significantly associated with T2DM in all genetic models: allele model (OR = 1.27, 95% confidence interval (CI) = 1.13-1.42), dominant model (OR = 1.19, 95% CI = 1.05-1.35), homozygote model (OR = 1.82, 95% CI = 1.38-2.39), and recessive model (OR = 1.75, 95% CI = 1.35-2.28), with minimal heterogeneity and no indication of publication bias. Similar associations with T2DM were also found for rs62589000 (p.P1019P) and 3'UTR ins/del, although the data was obtained from a small number of studies. For the other two polymorphisms rs1137100 (p.R109K) and rs8179183 (p.K656N), they were not significantly associated with T2DM. Our results provide robust evidences for the genetic association of rs1137101 (p.R223Q) in LEPR with T2DM susceptibility.

SUBMITTER: Yang MM

PROVIDER: S-EPMC4852360 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Variations in the Obesity Gene "LEPR" Contribute to Risk of Type 2 Diabetes Mellitus: Evidence from a Meta-Analysis.

Yang Ming Ming MM Wang Jun J Fan Jiao Jie JJ Ng Tsz Kin TK Sun Dian Jun DJ Guo Xin X Teng Yan Y Li Yan-Bo YB

Journal of diabetes research 20160418

Leptin is a hormone protein regulating food intake and energy expenditure. A number of studies have evaluated the genetic effect of leptin (LEP) and leptin receptor (LEPR) genes on T2DM. This study aimed to investigate the association between these gene polymorphisms and T2DM by a systematic review and meta-analysis. Published studies were identified through extensive search in PubMed and EMBASE. A total of 5143 T2DM cases and 5021 controls from 14 articles were included in this study. Five func ...[more]

PMID: 27195302

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Project description:BackgroundLeptin 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.MethodsA 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.ResultsFor 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 α = 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 α 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.ConclusionsThe present meta-analysis did not detect significant genetic associations between LEPR Q223R and K109R polymorphisms and T2D risk.

Project description:This systematic review aimed to evaluate the effectiveness and safety of probiotics for glycemic control in adults with impaired glucose control, including prediabetes and type 2 diabetes mellitus (T2DM). We searched PubMed, Embase, and Cochrane databases, and trial registries up to February 2019. We included randomized controlled trials (RCTs) of participants with prediabetes or T2DM. Eligible trials compared probiotics versus either placebo, no intervention, or comparison probiotics, or compared synbiotics versus prebiotics. Primary outcomes were mean change in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) from baseline to short term (<12 wk) and long term (≥12 wk). We performed meta-analyses using the random-effects model. We included 28 RCTs (1947 participants). Overall, probiotics reduced FBG more than the placebo/no intervention group with a mean difference (MD) of -12.99 mg/dL (95% CI: -23.55, -2.42; P value: 0.016) over the short term; and -2.99 mg/dL (95% CI: -5.84, -0.13; P value: 0.040) over the long term. There was also some evidence for reduced HbA1c in the probiotics group at both short term (MD: -0.17; 95% CI: -0.37, 0.02; P value: 0.084) and long term (MD: -0.14; 95% CI: -0.34, 0.06; P value: 0.172), however, these did not reach statistical significance possibly because only a few trials reported HbA1c as an outcome. Subgroup analyses showed a greater reduction in HbA1c in participants not receiving insulin therapy than those receiving insulin therapy. Furthermore, the effect of probiotics on the reduction of FBG was more pronounced in participants with FBG >130 mg/dL and those not receiving insulin therapy than their counterparts. Probiotics were also effective in lowering serum cholesterol over the short and long term. In conclusion, we found that probiotics may have a glucose-lowering effect in T2DM participants. The effect appeared to be stronger in participants with poorly controlled diabetes and those not on insulin therapy. Systematic review registration: CRD42019121682.

Dataset Information

Variations in the Obesity Gene "LEPR" Contribute to Risk of Type 2 Diabetes Mellitus: Evidence from a Meta-Analysis.

Publications

Variations in the Obesity Gene "LEPR" Contribute to Risk of Type 2 Diabetes Mellitus: Evidence from a Meta-Analysis.

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