Functional characterization of a novel p.Ser76Thr variant in IGFBP4 that associates with body mass index in American Indians.

ABSTRACT: Insulin-like growth factor binding protein 4 (IGFBP4) is involved in adipogenesis, and IGFBP4 null mice have decreased body fat through decreased PPAR-γ expression. In the current study, we assessed whether variation in the IGFBP4 coding region influences body mass index (BMI) in American Indians who are disproportionately affected by obesity. Whole exome sequence data from a population-based sample of 6779 American Indians with longitudinal measures of BMI were used to identify variation in IGFBP4 that associated with BMI. A novel variant that predicts a p.Ser76Thr in IGFBP4 (Thr-allele frequency = 0.02) was identified which associated with the maximum BMI measured during adulthood (BMI 39.8 kg/m² for Thr-allele homozygotes combined with heterozygotes vs. 36.2 kg/m²

SUBMITTER: Muller YL 

PROVIDER: S-EPMC9554187 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature