title: 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: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors: Alison M
authors: AM
authors: Mondul
authors: Kai
authors: K
authors: Yu
authors: William
authors: W
authors: Wheeler
authors: Hong
authors: H
authors: Zhang
authors: Stephanie J
authors: SJ
authors: Weinstein
authors: Jacqueline M
authors: JM
authors: Major
authors: Marilyn C
authors: MC
authors: Cornelis
authors: Satu
authors: S
authors: Männistö
authors: Aditi
authors: A
authors: Hazra
authors: Ann W
authors: AW
authors: Hsing
authors: Kevin B
authors: KB
authors: Jacobs
authors: Heather
authors: H
authors: Eliassen
authors: Toshiko
authors: T
authors: Tanaka
authors: Douglas J
authors: DJ
authors: Reding
authors: Sara
authors: S
authors: Hendrickson
authors: Luigi
authors: L
authors: Ferrucci
authors: Jarmo
authors: J
authors: Virtamo
authors: David J
authors: DJ
authors: Hunter
authors: Stephen J
authors: SJ
authors: Chanock
authors: Peter
authors: P
authors: Kraft
authors: Demetrius
authors: D
authors: Albanes
mesh_terms: D000368:Aged; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D014801:Vitamin A / Q000097:blood*
chemical_list: D014801:Vitamin A