Abstract
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 I2-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 polymorphism of ghrelin gene may be protective against T2DM in Caucasians, while predisposing to T2DM in Asians.
Highlights
Type 2 diabetes mellitus (T2DM), the most common metabolic disease, is characterized by a progressive decline in pancreatic βcell function and increase in insulin resistance
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%confidence intervals (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, while decreased in Caucasians
Summary
Type 2 diabetes mellitus (T2DM), the most common metabolic disease, is characterized by a progressive decline in pancreatic βcell function and increase in insulin resistance. There are two major forms of ghrelin in the blood, including acyl ghrelin and des-acyl ghrelin, in which about 80–90% of circulating ghrelin exists in des-acyl form, while only the acylated form was demonstrated to be biologically active (Hosoda et al, 2000) Both ghrelin and its receptor were found widely expressed in peripheral tissues and brain, exert important roles including stimulating gastric acid secretion, regulating glucose and lipid metabolism, and modulating learning and memory functions (Muller et al, 2015; Alamri et al, 2016; Hsu et al, 2016). The Leu72Met polymorphism of ghrelin gene has been associated with genetic predisposition to type 2 diabetes mellitus (T2DM), while conclusions remain conflicting We performed this updated meta-analysis to clarify the association between Leu72Met polymorphism and T2DM susceptibility
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