Association of GHRL and GHSR Gene Polymorphisms with Type 2 Diabetes Mellitus Susceptibility and Metabolic characteristics: A case–control study in an Iraqi population

Abstract

Type 2 diabetes mellitus (T2DM) is multifactorial, genetically predisposes and influenced by environment. The ghrelin (GHRL) and ghrelin receptor (GHSR) genes are related to appetite, insulin release, glucose metabolism and may be associated with susceptibility to T2DM. The aim of this study was the relationship between the GHRL rs3755777 and the GHSR rs495225 and rs572169 polymorphisms and T2DM risk and biochemical parameters in Iraqi population. This case–control study comprised 100 T2DM patients and 51 healthy controls. TaqMan™ SNP Genotyping was used for genotyping. The genotype and allele frequencies, Hardy–Weinberg equilibrium, genetic models, and multivariable logistic regression adjusted for age and sex were analyzed. There was difference in the genotype and allele distribution of the loci rs3755777 and rs495225. The T allele of rs3755777 showed a protective association under the dominant (OR = 0.22, 95% CI: 0.09–0.51) and allelic (OR = 0.43, 95% CI: 0.27–0.70) models. The allelic association of rs572169 was weak and didn't show an independent association in the multivariable model. Within the T2DM group, the differences in biochemical parameters by genotype weren't statistically significant following correction for multiple comparisons, the nominal association between rs495225 genotype and HDL-C was explored. The BMI adjusted sensitivity analysis revealed a high association of BMI and T2DM, while the individual SNP associations were reduced. The results indicate that genetic polymorphisms of GHRL and GHSR may play a role in the susceptibility to T2DM in this Iraqi population, but the results need to be confirmed in larger and independent population.