饮食、生活方式和基因与年龄相关性黄斑变性的联合关联
Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration.
作者信息
Meyers Kristin J, Liu Zhe, Millen Amy E, Iyengar Sudha K, Blodi Barbara A, Johnson Elizabeth, Snodderly D Max, Klein Michael L, Gehrs Karen M, Tinker Lesley, Sarto Gloria E, Robinson Jennifer, Wallace Robert B, Mares Julie A
机构信息
Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, New York.
出版信息
Ophthalmology. 2015 Nov;122(11):2286-94. doi: 10.1016/j.ophtha.2015.07.029. Epub 2015 Sep 6.
PURPOSE
Unhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated.
DESIGN
Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later.
PARTICIPANTS
Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663).
METHODS
Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively.
MAIN OUTCOME MEASURES
AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD.
RESULTS
The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score.
CONCLUSIONS
Having unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype.
目的
不健康的生活方式与年龄相关性黄斑变性（AMD）的患病几率增加有关。这种关联是否会因AMD的遗传风险而改变尚不清楚，因此对此进行了研究。
设计
研究健康生活方式与AMD风险基因型之间的相互作用，并与6年后评估的AMD患病率相关联。
参与者
年龄相关性眼病研究中50至79岁的女性，有暴露因素和AMD数据（n = 1663）。
方法
根据1994年和1998年评估的健康饮食指数得分、身体活动（每周代谢当量任务小时数）和吸烟包年数，分配健康生活方式得分（0 - 6分）。遗传风险基于补体因子H（CFH）中的Y402H和年龄相关性黄斑病变易感位点2（ARMS2）中的A69S。分别使用协同指数和乘法相互作用项评估比值比中的加性和乘性相互作用。
主要观察指标
通过对2001 - 2004年拍摄的立体眼底照片进行分级，评估AMD的存在和严重程度。337名女性患有AMD，其中91%患有早期AMD。
结果
健康生活方式得分低（0 - 2分）且CFH基因型为高风险（CC）的女性患AMD的几率是遗传风险低（TT）且健康生活方式得分高（4 - 6分）的女性的3.3倍（95%置信区间[CI]，1.8 - 6.1）。在整个样本中，没有显著的加性（协同指数[SI]，1.08；95% CI，0.70 - 1.67）或乘性（P相互作用 = 0.94）相互作用。然而，当将样本限制为在AMD评估前饮食稳定的女性（n = 728）时，与健康生活方式得分低和CFH基因型高风险相关的AMD几率增强（比值比，4.6；95% CI，1.8 - 11.6），且协同指数显著（SI，1.34；95% CI，1.05 - 1.70）。对饮食中的叶黄素和玉米黄质进行调整后，这种联合关联减弱，因此部分得到了解释。ARMS2与生活方式得分之间没有显著的加性或乘性相互作用。
结论
不健康的生活方式和两个CFH风险等位基因会增加AMD风险（主要在早期阶段），呈相加或更大（协同）的方式。然而，无论AMD风险基因型如何，不健康的生活方式都会增加AMD风险。
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