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J Clin Endocrinol Metab. 2007 Sep;92(9):3660-6. Epub 2007 Jun 12.

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

Author information

1
Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94143-0794, USA. chengi@humgen.ucsf.edu

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.

PMID:
17566087
DOI:
10.1210/jc.2007-0790
[Indexed for MEDLINE]

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