Insulin-like growth factor pathway polymorphisms associated with body size in Hispanic and non-Hispanic white women

Polymorphisms affecting insulin-like growth factors (IGF), their binding proteins (IGFBP), insulin receptor substrates (IRS), and other IGF regulatory molecules may affect growth, obesity, and obesity-related diseases, including cancer. The objective of this study was to better describe the associations between several IGF pathway variants and body size. Hispanic (n = 462) and non-Hispanic White (n = 1,702) women were recruited as controls in collaborative population-based case-control studies in Arizona, New Mexico, Colorado, Utah, and California. Body size measurements were taken by trained interviewers; genotypes were determined for the IGF1 CA repeat, the IGFBP3 -202 C > A substitution, the IRS1 G972R and IRS2 G1057D substitutions, and the vitamin D receptor (VDR) BsmI and FokI polymorphisms. Two associations were observed that were consistent in both Hispanics and non-Hispanic Whites: IGF1 CA repeat alleles of length other than 19 were associated with higher mean waist-to-hip ratios (WHR), P = 0.01, and women who carried an IGFBP3 A allele, compared with women with the CC genotype, more often reported high birthweight (odds ratio, 1.9; 95% confidence interval, 1.1-3.2). We observed trends for associations between IGFBP3 A allele and taller height, IRS1R allele, and smaller WHR, and VDR FokI ff genotype and larger WHR; each of these trends was present in only one ethnic group, and heterogeneity of effect by ethnicity was detected. These results provide evidence that IGF pathway polymorphisms have functional effects on growth and central obesity and indicate that genotype-phenotype relationships are ethnic specific.