Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson's disease risk in a Polish PD cohort
Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson's disease risk in a Polish PD cohort
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DOI：
10.1007/s00702-008-0121-9
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发表时间：
2008-11-01
影响因子：
3.3
通讯作者：
Zekanowski, Cezary
中科院分区：
文献类型：
--
作者：
Gaweda-Walerych, Katarzyna;Maruszak, Aleksandra;Zekanowski, Cezary
mtDNA常见变异被不一致地报道为改变帕金森病（PD）的风险。我们在241名PD患者和277名对照受试者中评估了线粒体单倍群、亚单倍群、编码和非编码单核苷酸多态性对PD风险的影响。按性别分层后，我们发现单倍型J（OR 0.19; 95%CI 0.069-0.53; P = 0.0014）与男性PD风险较低相关。出乎意料的是，基于控制区（CR）多态性的亚单倍群分析表明，亚群K1 a在健康对照中更普遍，而K1 c在PD患者中更常见（分别为P = 0.025和P = 0.011;双尾Fisher精确检验）。此外，我们证实了先前提出的部分解偶联氧化磷酸化（OXPHOS）的亚系（U4 + U 5a 1 + K+ J1 c + J2）降低PD风险的假设（P = 0.027，χ 2，经Yates校正）。推测解偶联mtDNA对PD的保护作用可能是由于减少了活性氧的产生。我们建议，分层成亚单倍型组或性别可能是必要的，以揭示参与特定的线粒体DNA亚系在PD发病机制。
mtDNA common variation is inconsistently reported to modify the risk of Parkinson's disease (PD). We evaluated the impact of the mitochondrial haplogroups, subhaplogroups, coding and non-coding single-nucleotide polymorphisms on PD risk in 241 PD patients and 277 control subjects. After stratification by gender, we found that haplogroup J (OR 0.19; 95% CI 0.069-0.53; P = 0.0014) was associated with a lower PD risk in males. Unexpectedly, subhaplogroup analysis based on the control region (CR) polymorphisms demonstrated that subcluster K1a was more prevalent in healthy controls, while K1c was more frequent in PD patients (P = 0.025 and P = 0.011, respectively; two-tailed Fisher's exact test). Additionally, we confirmed the hypothesis that sublineages (U4 + U5a1 + K+J1c + J2), previously proposed to partially uncouple oxidative phosphorylation (OXPHOS), decrease PD risk (P = 0.027, chi(2) with Yates' correction). The putative protective effect of uncoupling mtDNAs against PD might result from decreased production of reactive oxygen species. We propose that stratification into subhaplogroups or by gender could be necessary to reveal the involvement of specific mtDNA sublineages in PD pathogenesis.