Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
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DOI：
10.1186/1471-2350-14-4
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发表时间：
2013-01-09
影响因子：
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通讯作者：
Udar, Nitin
中科院分区：
文献类型：
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作者：
Kenney, M. Cristina;Hertzog, Dieter;Udar, Nitin
背景：老年性黄斑变性(AMD)是老年高加索人群视力丧失的主要原因。有强有力的证据表明，线粒体功能障碍和氧化应激在AMD视网膜细胞死亡中发挥了作用。本研究的目的是研究高加索人线粒体JTU单倍群与AMD的相关性。我们还利用已知的高危核基因SNPs ARMS2/LOC387715(G&gT；Ala69Ser，rs10490924)和CFH(T>；C；Try402His，rs1061170)对性别偏见和加性风险进行了评估。方法：提取162名AMD患者和164名年龄匹配的对照组的总DNA。采用聚合酶链式反应和限制性内切酶酶切技术检测J、U、T、H线粒体单倍群以及ARMS2-rs10490924和CFH-rs1061170 SNPs。结果：34%(55/162)的AMD患者存在JTU单倍群，15%(24/164)的AMD患者存在JTU单群突变(OR=2.99；p=0.0001)。男性的这种关联性(OR=3.98，p=0.005)略大于女性(OR=3.02，p=0.001)。在假设为显性效应的情况下，ARMS2(rs10490924；p=0.00001)和CFH(rs1061170；p=0.027)SNPs的风险等位基因与总的AMD人群显著相关。我们发现在JTU单倍群背景上ARMS2(Rs10490924)或CFH(Rs1061170)SNPs不存在相加风险。结论：JTU单倍群与AMD有很强的相关性。在我们的南加州人群中，ARMS2(Rs10490924)和CFH(Rs1061170)基因与AMD显著但独立相关。定义JTU线粒体单倍群簇的SNP可能改变视网膜的生物能量学，在AMD的发病机制中发挥重要作用。
Background: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924) and CFH (T > C; Try402His, rs1061170).Methods: Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene.Results: The JTU haplogroup cluster occurred in 34% (55/162) of AMD subjects versus 15% (24/164) of normal (OR = 2.99; p = 0.0001). This association was slightly greater in males (OR = 3.98, p = 0.005) than the female population (OR = 3.02, p = 0.001). Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001) and CFH (rs1061170; p = 0.027) SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924) or CFH (rs1061170) SNPs on the JTU haplogroup background.Conclusions: There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924) and CFH (rs1061170) genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD.