Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53726, USA.
Invest Ophthalmol Vis Sci. 2013 Mar 28;54(3):2333-45. doi: 10.1167/iovs.12-10867.
To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study.
1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression.
Twenty-one SNPs from 11 genes were associated with MPOD (P ≤ 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (βA = 0.029, P = 2.2 × 10(-4)). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10(-11)).
Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD.
研究来自于年龄相关性眼病研究（CAREDS）的女性中黄斑色素光学密度（MPOD）的遗传决定因素，该研究是妇女健康倡议观察研究的一个辅助研究。
2005 年 CAREDS 研究的 2005 名参与者中，有 1585 名使用定制的异色调闪烁光度法非侵入性地测量了黄斑色素光学密度（MPOD），并对与直接或通过脂质转运吸收、转运、结合和分解类胡萝卜素相关的 26 个候选基因中的 440 个单核苷酸多态性（SNP）进行了血液样本基因分型。使用最小二乘线性回归，逐个测试 SNP 与 MPOD 的相关性。
在调整叶黄素和玉米黄质的饮食摄入量后，有 21 个 SNP 来自 11 个基因与 MPOD 相关（P ≤ 0.05）。这包括与黄斑中玉米黄质结合相关的基因（GSTP1）、类胡萝卜素分解（BCMO1）、胆固醇转运或摄取（SCARB1、ABCA1、ABCG5 和 LIPC）、长链 ω-3 脂肪酸状态（ELOVL2、FADS1 和 FADS2）以及各种黄斑病变（ALDH3A2 和 RPE65）相关的变体。与 BCMO1 附近的 rs11645428 关联最强（βA=0.029，P=2.2×10(-4)）。对基因内的条件建模以及对包括腰围、糖尿病和纤维饮食摄入量在内的其他 MPOD 预测因素的进一步调整，导致 10 个基因中的 13 个 SNP 与 MPOD 保持独立关联。这些单基因多态性的变异解释了 MPOD 可变性的 5%（P=3.5×10(-11)）。
我们的研究结果支持，MPOD 是一种多因素表型，与与类胡萝卜素转运、摄取和代谢相关的基因变异有关，独立于已知的饮食和健康因素对 MPOD 的影响。
