Is there a correlation between GAD2 gene-243 A>G polymorphism and obesity?

Abstract

Introduction: GAD2 gene encodes the glutamate decarboxylase enzyme which catalyses the transformation of glutamate into γ-aminobutyric acid, GABA. It is suggested that some polymorphic alleles of GAD2 gene, such as -243A>G, have an increased transcriptional effect compared with the wild type, which results in an increase of GABA in the hypothalamus with the subsequent increase of the neuropeptide Y, thus exacerbating the hunger centre and the appetite. The aim of this study was to observe an association between the -243A>G polymorphism with obesity, comparatively studying a group of obese patients and a group of patients with normal weight.

Patients and method: 127 patients were clinically evaluated in the Genetic and Endocrine Department of Children’s Emergency Clinical Hospital, Cluj. The patients were included in two study groups, case group, with obesity (BMI higher than 97 kg/m2) and control group, with normal weight (BMI less than 97 kg/m2). Genotyping for GAD2-243A>G polymorphism was performed using PCR-RFLP technique, the two groups being compared regarding the genotypes and phenotypes.

Results and conclusions: In the obesity group, there is a statistically significant difference in BMI (kg/m2) between the subgroups with different genotypes (p=0.01), the AA genotype being less severely affected than AG and GG genotypes. In the normal weight group there is no association between BMI and different genotypes (AA, AG or GG). Also, there is a greater distribution of GG genotypes and G allele in the obesity group compared with the control group, with an odds ratio which suggest that -243A>G polymorphism is a risk factor in obesity development (GG genotype OR=3.76, G allele OR=1.73, p=0.04).

The finding of our study is important in explaining the multifactorial model of obesity, our research demonstrating that the GAD2-243 A> G variant could be a risk factor that added to other obesogenic factors would potentiate their effect.