Clinical Report 
A–243A→G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects
T. W. Boesgaard, S. I. Castella, G. Andersen, A. Albrechtsen, T. Sparso, K. Borch-Johnsen, T. Jorgensen, T. Hansen and O. Pedersen
Diabetic Medicine, 2007, 24(7), 702-706. DOI: 10.1111/j.1464-5491.2007.02110.x
Abstract
Aims The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the γ-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2−243A→G polymorphism and levels of body mass index (BMI) and estimates of glycaemia.
Methods Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2−243A→G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects.
Results The G-allele was associated with modestly lower BMI (P = 0.01). In a case–control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m
Conclusion The present study suggests that the GAD2−243A→G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.
ASCI-ID: 109-95
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