Insulin-Like Growth Factor Pathway Polymorphisms Associated with Body Size in Hispanic and Non-Hispanic White Women

Abstract

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 À202 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.

VDR and SRD5A2 Polymorphisms Combine to Increase Risk for Prostate Cancer in Both Non–Hispanic White and Hispanic White Men

“…For the V89L polymorphism, 52% and 44% of NHW and HW controls, respectively, had the VV genotype (P = 0.001). The genotype distributions in controls for these polymorphisms do not differ significantly from previously published results (31,32). Additionally, CDX2 genotype distributions in NHW controls are similar to what was found earlier (33).…”

Family-based association study of IGF1 microsatellites and height, weight, and body mass index

“…Consistent with our findings, several studies examining female White Caucasian populations did not find an association between 5¢CA-19 and height [22][23][24] or BMI, 22,25 or between 5¢CA-20 and height. 23 No association between 5¢CA-19 and BMI was found for Hispanic or Chinese women (although among Chinese women 5¢CA-17 was associated with lower BMI).…”

“…23 No association between 5¢CA-19 and BMI was found for Hispanic or Chinese women (although among Chinese women 5¢CA-17 was associated with lower BMI). 25,26 In a study from the Netherlands (Rotterdam), women homozygous for either 5¢CA-19 or 5¢CA-20 were significantly heavier than other homozygotes. 23 Another Netherlands (Amsterdam) study found that homozygous carriers of 5¢CA-19, 5¢CA-20 or 5¢CA-19/20 heterozygotes had significantly higher BMI than women with other genotypes, for one of two cohorts examined.…”

UCP2 A55V variant is associated with obesity and related phenotypes in an aboriginal community in Taiwan

“…36 Numerous conflicting studies show no evidence of UCP2 A55V association with obesity. 20,[22][23][24]26,37,38 Sweeney 39 found heterogeneity of genetic effects by ethnicity on growth and obesity and indicated that genotypephenotype relationships are ethnic specific. Linguistic, archeological and genetic evidence suggests insular populations exist throughout the Pacific region, including Polynesians, Micronesians and Taiwan aborigines.…”