Macular Pigment Research Group, Department of Chemical and Life Sciences, Waterford Institute of Technology, Waterford, Ireland.
Exp Eye Res. 2011 Nov;93(5):592-8. doi: 10.1016/j.exer.2011.07.005. Epub 2011 Jul 27.
Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk for this condition may be classified as genetic or environmental, with an interaction between such factors predisposing to this disease. This study investigated the relationship between AMD risk genes, macular pigment optical density (MPOD), which may protect against AMD, and serum concentrations of the macular carotenoids, lutein (L) and zeaxanthin (Z). This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. We also calculated MPOD Area as the area of MP under the spatial profile curve, to reflect MP across the macula. Serum L and Z were measured by HPLC. Genotyping of tag SNPs in the genes CFH, ARMS2, C3, C2 and BF was undertaken with multiplex polymerase chain reaction (PCR) and primer extension methodology (ABI Snapshot, ABI Warrington UK) on DNA extracted from peripheral blood. The mean ± SD (range) age of the subjects in this study was 48 ± 11 (21-66) years. There was a statistically significant association between CFH genotype and family history of AMD, with subjects having two non-risk CFH haplotypes (n = 35), or one non-risk and one protective CFH haplotype (n = 33), being significantly more likely to have a negative family history of AMD (Pearson Chi square: p = 0.001). There was no significant association between the AMD risk genes investigated and either MPOD (One way ANOVA: p > 0.05) or serum concentrations of L or Z (One way ANOVA: p > 0.05, for both). Subjects who were homozygous for risk alleles of both CFH and ARMS2 (n = 4) had significantly lower MPOD at 0.5° and 1° retinal eccentricity (Independent samples t test: p < 0.05) and lower MPOD Area which approached statistical significance (Independent samples t test: p = 0.058), compared to other subjects (n = 291). In conclusion, this study did not detect an association between individual AMD risk genotypes and the putatively protective MP, or serum concentrations of its constituent carotenoids. However, the combination of homozygous risk alleles at both CFH and ARMS2 loci was associated with significantly lower MPOD centrally, despite comparable serum concentrations of the macular carotenoids. These findings suggest that the maculae of subjects at very high genetic risk of AMD represent a hostile environment for accumulation and/or stabilization of MP.
年龄相关性黄斑变性（AMD）是发达国家老年人失明的最常见原因，这种疾病的风险可分为遗传或环境因素，这些因素之间的相互作用可能导致这种疾病。本研究调查了 AMD 风险基因、可能预防 AMD 的黄斑色素光密度（MPOD）与黄斑类胡萝卜素叶黄素（L）和玉米黄质（Z）的血清浓度之间的关系。这是一项对 302 名健康成年受试者的横断面研究。通过食物频率问卷评估 L 和 Z 的饮食摄入量，并用定制的异质闪光光度计测量 MPOD。我们还通过 HPLC 测量血清 L 和 Z。使用多重聚合酶链反应（PCR）和引物延伸方法（ABI Snapshot，ABI Warrington UK）对来自外周血的 DNA 进行 CFH、ARMS2、C3、C2 和 BF 基因中的标记 SNP 进行基因分型。本研究中受试者的平均年龄 ± SD（范围）为 48 ± 11（21-66）岁。CFH 基因型与 AMD 的家族史之间存在统计学显著关联，具有两个非风险 CFH 单倍型（n = 35）或一个非风险和一个保护性 CFH 单倍型（n = 33）的受试者，AMD 的家族史显著为阴性（皮尔逊卡方：p = 0.001）。在所研究的 AMD 风险基因与 MPOD 之间（单因素方差分析：p > 0.05）或与 L 或 Z 的血清浓度之间（单因素方差分析：p > 0.05，均如此）均无显著关联。同时携带 CFH 和 ARMS2 风险等位基因的纯合子（n = 4）在 0.5°和 1°视网膜偏心度处的 MPOD 明显较低（独立样本 t 检验：p < 0.05），并且 MPOD Area 也接近统计学意义（独立样本 t 检验：p = 0.058），与其他受试者（n = 291）相比。总之，本研究未发现个体 AMD 风险基因型与假定保护性 MP 或其组成类胡萝卜素的血清浓度之间存在关联。然而，CFH 和 ARMS2 基因座的纯合风险等位基因的组合与中央 MPOD 明显降低相关，尽管黄斑类胡萝卜素的血清浓度相当。这些发现表明，AMD 遗传风险极高的受试者的黄斑区代表了一个不利于 MP 积累和/或稳定的恶劣环境。
