Journal Article

Genome-wide association study of circulating retinol levels

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 and Demetrius Albanes

in Human Molecular Genetics

Volume 20, issue 23, pages 4724-4731
Published in print December 2011 | ISSN: 0964-6906
Published online August 2011 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr387

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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.

Journal Article.  3945 words.  Illustrated.

Subjects: Genetics and Genomics

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