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

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  • Yunzhong Yang
  • Tianhua Niu

Abstract

Background: 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. Methods: 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. Results: 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 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. Conclusions: The present meta-analysis did not detect significant genetic associations between LEPR Q223R and K109R polymorphisms and T2D risk.

Suggested Citation

  • Yunzhong Yang & Tianhua Niu, 2018. "A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk," PLOS ONE, Public Library of Science, vol. 13(1), pages 1-25, January.
    • Handle: RePEc:plo:pone00:0189366
    DOI: 10.1371/journal.pone.0189366
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    References listed on IDEAS

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    1. Nicole Bender & Noëmi Allemann & Diana Marek & Peter Vollenweider & Gérard Waeber & Vincent Mooser & Matthias Egger & Murielle Bochud, 2011. "Association between Variants of the Leptin Receptor Gene (LEPR) and Overweight: A Systematic Review and an Analysis of the CoLaus Study," PLOS ONE, Public Library of Science, vol. 6(10), pages 1-14, October.
    2. Qi Wang & Shao-Bo Zhou & Li-Jie Wang & Ming-Ming Lei & Yong Wang & Chi Miao & Yuan-Zhe Jin, 2014. "Seven Functional Polymorphisms in the CETP Gene and Myocardial Infarction Risk: A Meta-Analysis and Meta-Regression," PLOS ONE, Public Library of Science, vol. 9(2), pages 1-12, February.
    3. He-Ling Wang & Ping-Yi Zhou & Peng Liu & Yu Zhang, 2014. "ALDH2 and ADH1 Genetic Polymorphisms May Contribute to the Risk of Gastric Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-11, March.
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    1. Hang Su & Na Rei & Lei Zhang & Jiaxiang Cheng, 2018. "Meta-analyses of IL1A polymorphisms and the risk of several autoimmune diseases published in databases," PLOS ONE, Public Library of Science, vol. 13(6), pages 1-18, June.

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