title: 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.
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; The Centre for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150001, China; Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin 999077, Hong Kong.
authors.forename: Ming Ming
authors.initials: MM
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jun
authors.identifier: 0000-0003-3653-6803
authors.initials: J
authors.lastname: Wang
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jiao Jie
authors.initials: JJ
authors.lastname: Fan
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin 999077, Hong Kong.
authors.forename: Tsz Kin
authors.identifier: 0000-0001-7863-7229
authors.initials: TK
authors.lastname: Ng
authors.affiliation: The Centre for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150001, China.
authors.forename: Dian Jun
authors.initials: DJ
authors.lastname: Sun
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Li
mesh_terms: D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D054411:Receptors, Leptin / Q000235:genetics*
chemical_list: C515448:LEPR protein, human; D054411:Receptors, Leptin