GENETIC-STUDIES OF POLYMORPHISMS IN 10 NON-INSULIN-DEPENDENT DIABETES-MELLITUS CANDIDATE GENES IN TAMIL INDIANS FROM PONDICHERY

We report a study of 10 candidate genes presumably involved in diabete s or insulin resistance or obesity among Pondicherian Tamil Indians, a n isolated population with a high prevalence of diabetes. Forty-nine f amilies with at least two affected patients in the sibship (567 indivi duals) were selected and tested by PCR-RFLP techniques for reported mu tations in 10 diabetes or obesity candidate genes:glucagon receptor, i nsulin receptor substrate 1, insulin receptor, human beta 3 adrenergic receptor, fatty acid binding protein 2, mitochondrial tRNA(Leu(UUR)), sulphonylurea receptor, human uncoupling protein and the glycogen-ass ociated regulatory subunit of protein phosphatase-1 Glucokinase gene w as also screened for mutations. No mutations were found in glucokinase , glucagon receptor and mitochondrial genes in any of the 49 probands. Frequencies of polymorphisms at other loci were similar to those repo rted in Caucasian populations, except for 4 of the loci at which a hig her frequency of variants was observed : human beta 3 adrenergic recep tor, human uncoupling type 1 protein, fatty acid binding protein 2 and the glycogen-associated regulatory subunit of protein phosphatase-l. However, no evidence of association between any of these gene variants and non-insulin-dependent diabetes mellitus (NIDDM) or quantitative t raits related to NIDDM (including body mass index, waist/hip ratio, in sulinaemia, glycaemia, triglycerides and total cholesterol) was found in our sample. These results suggest th at none of these gene variants commonly found in the Pondicherian Tamil population of South India is a major NIDDM predisposing locus, although it cannot he excluded that they may contribute to the polygenic background of the metabolic synd rome in Pondichery.