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.
Hum Mol Genet. 2011 Dec 1;20(23):4724-31. doi: 10.1093/hmg/ddr387. Epub 2011 Aug 30.
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.
视黄醇是维生素 A 中最具生物活性的形式之一，据推测它会影响多种人类疾病，包括哮喘、心血管疾病、传染病和癌症。我们对来自两个男性队列的 5006 名白种人进行了全基因组关联研究：α-生育酚、β-胡萝卜素癌症预防研究（ATBC）和前列腺、肺、结直肠和卵巢（PLCO）癌症筛查试验。我们确定了与循环视黄醇水平相关的两个独立的单核苷酸多态性，它们位于转甲状腺素蛋白（TTR）和视黄醇结合蛋白 4（RBP4）基因附近，这两个基因编码视黄醇的主要载体蛋白：rs1667255（P =2.30×10(-17)) 和 rs10882272（P =6.04×10(-12))。我们在来自护士健康研究和因奇安蒂老龄化研究（InCHIANTI）的独立样本中复制了与 rs10882272 在 RBP4 中的关联，该研究包括 3792 名女性和 504 名男性（P =9.49×10(-5))，但在女性中没有发现与 rs1667255 在 TTR 中与视黄醇的关联，因此表明存在性别二态性的证据（P 交互作用=1.31×10(-5))。发现与血清视黄醇水平相关的常见遗传变异可能为视黄醇和其他维生素 A 化合物对癌症和其他复杂疾病的发展的贡献提供进一步的见解。
