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

Yunzhong Yang,Tianhua Niu,Roberto Amendola

doi:10.1371/journal.pone.0189366

Abstract

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.

Highlights

Type 2 diabetes (T2D), a metabolic disorder that is characterized by hyperglycemia in the context of insulin resistance and a relative lack of insulin, is the most common form of diabetes, accounting for at least 90% of diabetic individuals globally [1]
Q223R was not significantly associated with type 2 diabetes (T2D) risk (OR = 1.09, 95% confidence intervals (CIs): 0.80–1.48, P-value = 0.5989), which was consistent with results obtained under four genotypic models
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

Summary

Introduction

Type 2 diabetes (T2D), a metabolic disorder that is characterized by hyperglycemia (i.e., high blood glucose) in the context of insulin resistance and a relative lack of insulin, is the most common form of diabetes, accounting for at least 90% of diabetic individuals globally [1]. LEP exerts its important physiological effect on the regulation of fat metabolism by binding to LEP receptor (LEPR, called CD295 and OBR) [6,7,8], which is a single transmembrane protein that belongs to class I cytokine receptor family distributed in a variety of tissue types [9]. Both LEP and LEPR genes have been cloned in humans [10, 11], and have been mapped to chromosome regions 7q32.1 [12] and 1p31.3 [13, 14], respectively. Various genetic association studies were performed to evaluate associations of LEPR genetic variants with type 2 diabetes (T2D) susceptibility

Methods

Results

Conclusion