GHRL Gene Leu72Met Polymorphism and Type 2 Diabetes Mellitus: A Meta-Analysis Involving 8,194 Participants

Abstract

Background: Although many studies indicate a positive correlation between GHRL gene Leu72Met polymorphism and an increased susceptibility to type 2 diabetes mellitus (T2DM), inconsistencies between independent studies still remain. Objective: Considering the inconsistencies between them, we have performed the current meta-analysis study. The objective of this study is to better examine the correlation of the GHRL gene Leu72Met polymorphism and T2DM. Methods: The current meta-analysis, involving 8,194 participants from 11 independent studies, was performed. A fixed effect model was used to evaluate the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs). Results: A significant association was found between T2DM and GHRL gene Leu72Met polymorphism under recessive (OR: 1.33, 95% CI: 1.01–1.76, P = 0.04), and homozygous genetic models (OR: 1.34, 95% CI: 1.01–1.78, P = 0.04) in the whole population. The correlation was more distinct in our subgroup analysis of the Chinese population under recessive (OR: 1.52, 95% CI: 1.07–2.15, P = 0.02), dominant (OR: 1.70, 95% CI: 1.38–2.10, P < 0.00001), additive (OR: 1.16, 95% CI: 1.02–1.33, P = 0.02), and homozygous genetic models (OR: 1.54, 95% CI: 1.07–2.20, P = 0.02). Conclusions: In short, GHRL gene Leu72Met polymorphism was significantly correlated with increased T2DM risk, particularly in the Chinese population. Individuals carrying the Met72 allele of GHRL Leu72Met gene polymorphism, particularly those of Chinese ancestry, may be more susceptible to developing T2DM disease.

Association of Pro-Ghrelin Leu72Met Polymorphism with Acylated Ghrelin Level and Alcohol Use Disorder: A Preliminary Study

“…In humans, the GHRL gene (Gene ID: 51738) is located in 3p25-26 and comprises 7 exons. The five exons code the precursor preproghrelin with 117 amino acids and exons 1 and 2 encode the functional 28 amino-acid region (3,(13)(14)(15). The GHRL gene is highly polymorphic and has non-coding or coding region SNPs (more than 300) (3).…”

“…The GHRL gene is highly polymorphic and has non-coding or coding region SNPs (more than 300) (3). Among them, the Leu72Met (+408C>A) polymorphism of the GHRL gene, located on the second exon, replaces the leucine at the 72 nd amino acid with a methionine by switching cytosine to adenine (15). The GHRL Leu72Met polymorphism does not change the sequence of mature ghrelin since it lies outside the region where the mature ghrelin protein is encoded.…”

“…Although its functional significance is still unknown, it is hypothesized that the GHRL Leu72Met polymorphism affects ghrelin secretion and activity by changing to protein synthesis or mRNA stability (14,15).…”

Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population

“…The association analysis with T2D, showed that 72Met allele and Leu72Met genotype were protective against T2D, but after the adjustment, only the 72Met allele remained associated, suggesting that the protective effect of Leu72Met is given by 72Met allele. To this respect, it has been described that the 72Met allele induces protection against T2D in Caucasians [13], whereas the opposite occurs in Asiatic and Danish populations [14,25,27,28]. Moreover, the 72Met allele has also, been associated as a protective against insulin resistance and body fat accumulation [26,29].…”

Genetic variation in DPP-IV gene linked to predisposition of T2DM: A case control study

“…The susceptibility to T2DM is determined by an interplay of genetic and metabolic factors [ 5 ]. Recently several genes ascertaining the existence of T2DM have garnered attention such as ABCA1 , SOD2, SLC30A8 , KCNJ11, ADIPOQ, TCF7L2 , IL-10 , PON2 , and DPP- IV [ 7 ].…”