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Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson’s disease risk in a Polish PD cohort
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Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson’s disease risk in a Polish PD cohort
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Journal Article
Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson’s disease risk in a Polish PD cohort
2008
Overview
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, χ
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.
Publisher
Springer Vienna,Springer Nature B.V
Subject
/ Age
/ Aged
/ DNA, Mitochondrial - genetics
/ Female
/ Females
/ Gender
/ Genotype
/ Humans
/ Male
/ Medicine
/ Parkinson Disease - epidemiology
/ Parkinson Disease - genetics
/ Parkinson's Disease and Allied Conditions - Original Article
/ Polymorphism, Single Nucleotide - genetics
/ Risk
