Genome-wide association study of circulating retinol levels.

Abstract

Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10(-17)) and rs10882272 (P =6.04× 10(-12)). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10(-5)), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10(-5)). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

• Authors: Alison M Mondul, Kai Yu, William Wheeler, Hong Zhang, Stephanie J Weinstein, Jacqueline M Major, Marilyn C Cornelis, Satu Männistö, Aditi Hazra, Ann W Hsing, Kevin B Jacobs, Heather Eliassen, Toshiko Tanaka, Douglas J Reding, Sara Hendrickson, Luigi Ferrucci, Jarmo Virtamo, David J Hunter, Stephen J Chanock, Peter Kraft, Demetrius Albanes
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 20 Issue 23 Pg. 4724-31 (Dec 01 2011) ISSN: 1460-2083 [Electronic] England
• PMID: 21878437 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Vitamin A

Topics

• Aged
• Chromosomes, Human, Pair 18 (genetics)
• Cohort Studies
• Female
• Genome-Wide Association Study
• Humans
• Linkage Disequilibrium (genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Reproducibility of Results
• Vitamin A (blood)