Ethnicity-Specific Association Between Ghrelin Leu72Met Polymorphism and Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis

Background: The Leu72Met polymorphism of ghrelin gene has been associated with genetic predisposition to type 2 diabetes mellitus (T2DM), while conclusions remain conflicting. Hence, we performed this updated meta-analysis to clarify the association between Leu72Met polymorphism and T2DM susceptibility. Methods: Six electronic databases were consulted for articles published before 1 January, 2018. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated under five genetic models to assess this association. We used I-2-test and Q statistics to measure heterogeneity across the included studies. Subgroup analyses and publication bias were also performed. Results: Thirteen case-control studies involving 4720 T2DM patients and 4206 controls were included in this meta-analysis. The overall results using fixed-effects models showed that Leu72Met polymorphism was significantly associated with an increased risk of T2DM under homozygous model (OR = 1.307, 95% CI 1.001-1.705, p = 0.049). Further subgroup analyses stratified by ethnicity revealed that the risk for T2DM was only increased in Asians (homozygous model: OR = 1.335, 95% CI 1.014-1.758, p = 0.040), while decreased in Caucasians (dominant model: OR = 0.788, 95% CI 0.635-0.978, p = 0.030; heterozygous model: OR = 0.779, 95% CI 0.626-0.969, p = 0.025; allelic model: OR = 0.811, 95% CI 0.661-0.995, p = 0.045). Funnel plots were basically symmetrical, and all p-values of Egger's test under five genetic models were >0.050, which indicated no evidence of publication bias. Conclusions: Our results demonstrate that the Leu72Met polymorphismof ghrelin gene may be protective against T2DM in Caucasians, while predisposing to T2DM in Asians.