Mitochondrial Variation and the Risk of Age-Related Macular Degeneration Across Diverse Populations
Mitochondrial Variation and the Risk of Age-Related Macular Degeneration Across Diverse Populations
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DOI：
10.1142/9789814644730_0024
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发表时间：
2014-11
影响因子：
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通讯作者：
Nicole A. Restrepo;S. Mitchell;Robert J. Goodloe;D. Murdock;J. Haines;D. Crawford
中科院分区：
文献类型：
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作者：
Nicole A. Restrepo;S. Mitchell;Robert J. Goodloe;D. Murdock;J. Haines;D. Crawford
在识别年龄相关性黄斑变性（AMD）的易感性变异方面已经取得了实质性进展。大多数鉴定与 AMD 相关的遗传变异的研究都集中在核遗传变异上。虽然有一些证据表明线粒体遗传变异会导致 AMD 易感性，但迄今为止，这些研究仅限于欧洲血统人群，导致缺乏不同人群的数据。环境相关基因流行病学结构 (EAGLE) 研究的一个主要目标是描述不同人群中常见、复杂疾病的潜在遗传结构。本研究旨在确定线粒体遗传变异是否影响不同人群的 AMD 风险。我们进行了一项遗传关联研究，以调查线粒体 DNA 变异对 AMD 风险的影响。我们获取了来自国家健康和营养检查调查的样本，这是一项以美国人口为基础的横断面调查，收集的数据不考虑健康状况。 AMD 病例和对照选自第三个 NHANES 和 NHANES 2007-2008 数据集，其中包括非西班牙裔白人、非西班牙裔黑人和墨西哥裔美国人。 AMD 病例被定义为年龄 > 60 岁的早期/晚期 AMD，通过眼底照相确定。对 63 个线粒体 SNP 进行了靶向基因分型，然后将参与者分为线粒体单倍群。我们使用逻辑回归假设显性遗传模型调整了年龄、性别、体重指数和吸烟状况（曾经与从未）。对单个 SNP 和线粒体单倍群 J、T 和 U 进行回归和荟萃分析。我们确定了 5 个与墨西哥裔美国人 AMD 相关的 SNP（p < 0.05），其中 3 个位于对照区域（mt16111、mt16362 和 mt16319），1 个位于 MT-RNR2（mt1736），1 个位于 MT-ND4 （MT12007）。在最终的荟萃分析中，非西班牙裔黑人或非西班牙裔白人中没有线粒体变异或单倍群显着相关。这项研究进一步证明线粒体变异在 AMD 易感性中发挥作用，并有助于了解墨西哥裔美国人 AMD 的遗传结构。
Substantial progress has been made in identifying susceptibility variants for age-related macular degeneration (AMD). The majority of research to identify genetic variants associated with AMD has focused on nuclear genetic variation. While there is some evidence that mitochondrial genetic variation contributes to AMD susceptibility, to date, these studies have been limited to populations of European descent resulting in a lack of data in diverse populations. A major goal of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study is to describe the underlying genetic architecture of common, complex diseases across diverse populations. This present study sought to determine if mitochondrial genetic variation influences risk of AMD across diverse populations. We performed a genetic association study to investigate the contribution of mitochondrial DNA variation to AMD risk. We accessed samples from the National Health and Nutrition Examination Surveys, a U.S population-based, cross-sectional survey collected without regard to health status. AMD cases and controls were selected from the Third NHANES and NHANES 2007-2008 datasets which include non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. AMD cases were defined as those > 60 years of age with early/late AMD, as determined by fundus photography. Targeted genotyping was performed for 63 mitochondrial SNPs and participants were then classified into mitochondrial haplogroups. We used logistic regression assuming a dominant genetic model adjusting for age, sex, body mass index, and smoking status (ever vs. never). Regressions and meta-analyses were performed for individual SNPs and mitochondrial haplogroups J, T, and U. We identified five SNPs associated with AMD in Mexican Americans at p < 0.05, including three located in the control region (mt16111, mt16362, and mt16319), one in MT-RNR2 (mt1736), and one in MT-ND4 (mt12007). No mitochondrial variant or haplogroup was significantly associated in non-Hispanic blacks or non- Hispanic whites in the final meta-analysis. This study provides further evidence that mitochondrial variation plays a role in susceptibility to AMD and contributes to the knowledge of the genetic architecture of AMD in Mexican Americans.