INS VNTR is not associated with childhood obesity in 1,023 families:: A family-based study

Previous studies have described genetic associations of the insulin gene variable number tandem repeat ( INS VNTR) variant with childhood obesity and associated phenotypes. We aimed to assess the contribution of INS VNTR genotypes to childhood obesity and variance of insulin resistance, insulin secretion, and birth weight using family-based design. Participants were either French or German whites. We used transmission disequilibrium tests (TDTs) for assessing binary traits and quantitative pedigree disequilibrium tests for assessing continuous traits. In contrast to previous findings, we did not observe any familial association with childhood obesity ( T = 50%, P = 0.77) in the 1,023 families tested. In French obese children, INS VNTR did not associate with fasting insulin levels ( P = 0.23) and class I allele showed only borderline association with increased insulin secretion index at 30 min ( P = 0.03). INS VNTR did not associate with birth weight in obese children ( P = 0.98) and TDT analyses in 350 French families with history of low birth weight ( LBW) showed no association with this condition ( P = 0.92). In summary, our study, the largest performed so far, does not support the previously reported associations between INS VNTR and childhood obesity, insulin resistance, or birth weight, and does not suggest any major role for this variant in modulating these traits.