Genetic determinants of circulating insulin-like growth factor (IGF)-I, IGF binding protein (BP)-1, and IGFBP-3 levels in a multiethnic population

J Clin Endocrinol Metab. 2007 Sep;92(9):3660-6. doi: 10.1210/jc.2007-0790. Epub 2007 Jun 12.

Abstract

Context: Both circulating levels and genetic variation of IGFs have been associated with cancer risk, yet the relationship between the two is not well understood.

Objective: To investigate whether common genetic variation in IGF1, IGF binding protein 1 (IGFBP1), and IGFBP3 influences circulating levels of IGF-I, IGFBP-1, and IGFBP-3, we conducted a cross-sectional study of African-American, Native Hawaiian, Japanese-American, Latino, and white men and women in the Multiethnic Cohort.

Design: Plasma levels of IGF-I, IGFBP-1, and IGBFP-3 were measured by ELISA in a random sample of 837 Multiethnic Cohort participants. Previously identified tag single nucleotide polymorphisms (SNPs) for IGF1 (29 tag SNPs) and IGFBP1/IGFBP3 (23 tag SNPs) were genotyped among the 837 participants. Analysis of covariance was conducted to test for differences in mean IGF-I, IGFBP-1, and IGFBP-3 levels across respective IGF1, IGFBP1, and IGFBP3 genotypes, adjusting for previously identified dietary and lifestyle correlates.

Results: Five highly correlated IGFBP3 SNPs (rs3110697, rs2854747, rs2854746, rs2854744, and rs2132570) demonstrated strongly significant associations with IGFBP-3 levels when conservatively adjusted for multiple hypothesis testing (Bonferroni adjusted P trends = 7.75 x 10(-8) to 1.44 x 10(-5)). Patterns of associations were consistent across the five racial/ethnic groups.

Conclusion: In summary, our study suggests that common genetic variation in IGFBP3 influences circulating levels of IGFBP-3 among African-Americans, Native Hawaiians, Japanese-Americans, Latinos, and whites.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Ethnic Groups / genetics*
  • Female
  • Genotype
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / blood*
  • Insulin-Like Growth Factor Binding Protein 1 / genetics*
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Insulin-Like Growth Factor I / analysis*
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I