From the Department of Neuroscience (R.R.V., M.C.B., A.I.S.-B., R.L.W., S.K., S.F.R., R.R., D.W.D., O.A.R.), Division of Biomedical Statistics and Informatics (M.G.H., P.W.J.), Department of Neurology (R.J.U., Z.K.W.), and Department of Clinical Genomics (O.A.R.), Mayo Clinic, Jacksonville, FL; Perelman School of Medicine (E.S., J.Q.T., V.M.V.D.) and Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; and VIB-UAntwerp Center for Molecular Neurology (R.R.), University of Antwerp, Belgium.
Neurology. 2021 Mar 30;96(13):e1755-e1760. doi: 10.1212/WNL.0000000000011649. Epub 2021 Feb 10.
To determine whether stable polymorphisms that define mitochondrial haplogroups in mitochondrial DNA (mtDNA) are associated with Pick disease risk, we genotyped 52 pathologically confirmed cases of Pick disease and 910 neurologically healthy controls and performed case-control association analysis.
Fifty-two pathologically confirmed cases of Pick disease from Mayo Clinic Florida (n = 38) and the University of Pennsylvania (n = 14) and 910 neurologically healthy controls collected from Mayo Clinic Florida were genotyped for unique mtDNA haplogroup-defining variants. Mitochondrial haplogroups were determined, and in a case-control analysis, associations of mtDNA haplogroups with risk of Pick disease were evaluated with logistic regression models that were adjusted for age and sex.
No individual mtDNA haplogroups or superhaplogroups were significantly associated with risk of Pick disease after adjustment for multiple testing ( < 0.0021, considered significant). However, nominally significant ( < 0.05) associations toward an increased risk of Pick disease were observed for mtDNA haplogroup W (5.8% cases vs 1.6% controls, odds ratio [OR] 4.78, = 0.020) and subhaplogroup H4 (5.8% cases vs 1.2% controls, OR 4.82, = 0.021).
Our findings indicate that mtDNA variation is not a disease driver but may influence disease susceptibility. Ongoing genetic assessments in larger cohorts of Pick disease are currently underway.
为了确定线粒体 DNA（mtDNA）中定义线粒体单倍群的稳定多态性是否与匹克病的发病风险相关，我们对 52 例经病理证实的匹克病病例和 910 名神经科健康对照进行了基因分型，并进行了病例对照关联分析。
我们对来自佛罗里达梅奥诊所（n = 38）和宾夕法尼亚大学（n = 14）的 52 例经病理证实的匹克病病例和来自佛罗里达梅奥诊所的 910 名神经科健康对照进行了基因分型，以确定独特的 mtDNA 单倍群定义变体。确定了线粒体单倍群，并在病例对照分析中，使用逻辑回归模型评估 mtDNA 单倍群与匹克病发病风险的关联，该模型调整了年龄和性别因素。
在进行多次检验校正后（<0.0021，认为具有统计学意义），没有单个 mtDNA 单倍群或超单倍群与匹克病的发病风险显著相关。然而，mtDNA 单倍群 W（5.8%的病例 vs. 1.6%的对照，比值比[OR]4.78， = 0.020）和亚单倍群 H4（5.8%的病例 vs. 1.2%的对照，OR4.82， = 0.021）与匹克病发病风险增加呈显著关联（<0.05）。
我们的研究结果表明，mtDNA 变异不是疾病的驱动因素，但可能影响疾病的易感性。目前正在对更大的匹克病队列进行遗传评估。
