The insulin gene VNTR : associations and interactions with childhood body fat mass and insulin secretion

Context Polymorphism at the insulin gene (INS) VNTR shows variable associations with childhood BMI in different populations. Objective To study INS VNTR associations with body composition and insulin secretion in children. Design Prospective birth cohort study Participants 947 children genotyped for the INS VNTR Main outcome measures Whole body DXA at 9 years to estimate height-corrected fat mass index (FMI), truncal fat index (TFI) and fat-free mass (FFM). Insulin secretion post-oral glucose at 8y. Results Homozygous III/III children had higher BMI (p=0.020), FMI (p=0.015) and TFI (p=0.022) at 9y than class I bearers, but no difference in FFM (p=0.23). Gain in weight SD score between birth to 3y was positively associated with BMI, FMI and TFMI in class I bearers, but not in III/III children (p-interaction with genotype = 0.009 to 0.066). INS VNTR genotype was not overall associated with insulin secretion at 8y (p=0.64), but class I bearers showed a stronger positive correlation between insulin secretion and BMI at 8y (regression coefficient ± SE: 0.26±0.05, p<0.0001) than III/III children (-0.10±0.07, p=0.48) (p-interaction=0.003). Conclusion We clarified that the overall association between INS VNTR class III/III genotype and larger BMI in this population relates to fat mass, but not fat-free mass. In contrast, among the sub-group of children who showed rapid infancy weight gain, class I bearers tended to have larger BMI and fat mass than III/III children. This genetic interaction could relate to insulin secretion, which in class I bearers increased more rapidly with overweight and obesity. H A L athor m anscript inerm -005995, version 1