The insulin gene variable number of tandem repeat: Associations and interactions with childhood body fat mass and insulin secretion in normal children

Context: Polymorphism at the insulin gene (INS) variable number of tandem repeat (VNTR) shows variable associations with childhood body mass index (BMI) in different populations. Objective: The objective of this study was to observe INS VNTR associations with body composition and insulin secretion in children. Design: The study was designed as a prospective birth cohort study. Participants: A total of 947 children genotyped for the INS VNTR participated. Main Outcome Measures: Main outcome measures were whole body dual x-ray emission absorptiometry at 9 yr to estimate height-corrected fat mass index (FMI), truncal FMI, and fat-free mass, and insulin secretion after oral glucose at 8 yr. Results: Homozygous III/III children had higher BMI (P=0.020), FMI (P=0.015), and truncal FMI (P=0.022) at 9 yr than class I bearers, but no difference in fat-free mass (P=0.23). Gain in weight SD score between birth and 3 yr was associated positively with BMI, FMI, and truncal FMI in class I bearers, but not in III/III children (p-interaction with genotype =0.009-0.066). INS VNTR genotype was not associated overall with insulin secretion at 8 yr (P=0.64), but class I bearers showed a stronger positive correlation between insulin secretion and BMI at 8 yr ( 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 subgroup 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.