Running Head: INS VNTR is associated with insulin response to glucose in young obese.

We performed a genotype-phenotype association study to examine whether the insulin VNTR (INS VNTR) polymorphism located in the insulin gene promoter was associated with changes in insulin response to oral glucose. Two classes of INS VNTR alleles are observed in caucasians, the ‘short ’ Class I and the ‘long ’ Class III. Plasma insulin and glucose concentrations, and indices of insulin secretion (IGI) and sensitivity (ISI) were measured using an oral glucose tolerance test (OGTT) in 387 obese children aged 12 ± 0.1 yrs with a mean BMI of 30.6 kg/m2 (161 % of the normal mean). During OGTT, plasma insulin and IGI were 20-30 % higher in I/I obese children versus III carriers (P < 0.01). A general linear model adjusting for age, sex, and puberty was also used to evaluate the influence of the VNTR genotype on the BMI-IGI (P = 0.07) and the BMI-ISI (P < 0.006) relationships. The INS VNTR can therefore be considered an quantitative trait locus (QTL) influencing glucose-stimulated insulin physiology in obese juveniles. Keywords: Insulin gene, VNTR, QTL, insulin secretion, obesity, obese childre