The association between leptin receptor gene polymorphisms and type 2 diabetes mellitus: A systematic review and meta-analysis

Diabetes Res Clin Pract. 2016 Nov:121:49-58. doi: 10.1016/j.diabres.2016.08.008. Epub 2016 Aug 26.


Background: Several case-control studies have demonstrated a relationship between leptin receptor (LEPR) gene polymorphism and type 2 diabetes mellitus (T2DM) risk, though the results have not always been consistent among diverse populations. This meta-analysis was designed to assess a more accurate association between LEPR polymorphism and T2DM.

Methods: Eight electronic databases were consulted and researchers searched for Chinese and English peer-reviewed articles, published between 2000 and 2015, that referred to the association between LEPR polymorphism and T2DM. Pooled odds ratios (OR) with a 95% confidence interval (CI) were calculated in allele contrast, recessive, dominant and additive genetic models to assess this association.

Results: Four repeatedly reviewed polymorphisms, taken from 22 studies on Arg109Lys, Asn656Lys, Gln223Arg and Pro1019Pro with 31,260 controls and 25,560 cases, were included in the meta-analysis model. The meta-result demonstrated that only the Pro1019Pro polymorphism was substantially associated with T2DM risk-G vs. A: OR with 95% CI 0.58 (0.43-0.79), Z=3.51, p=0.0005; GG vs. AG+AA: 0.57 (0.42-0.77), Z=3.66, p=0.0002; GG+AG vs. AA: 0.55 (0.37-0.81), Z=3.01, p=0.003; GG vs. AA: 0.51 (0.37-0.69), Z=4.24, p<0.001.

Conclusions: Our meta-analysis suggested a significant association between the LEPR Pro1019Pro polymorphism and T2DM risk. Thus, targeted healthcare should be strengthened with regard to this gene carrier in order to prevent T2DM.

Keywords: LEPR; Meta-analysis; Polymorphism; T2DM.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alleles
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Polymorphism, Genetic*
  • Receptors, Leptin / genetics*
  • Risk


  • Receptors, Leptin