title: Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson's disease risk in a Polish PD cohort.
abstract: 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, chi2 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.
authors.affiliation: Department of Neurodegenerative Disorders, Medical Research Center Polish Academy of Sciences, Pawińskiego 5, 02-106, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gaweda-Walerych
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Maruszak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.forename: Monika
authors.initials: M
authors.lastname: Bialecka
authors.forename: Gabriela
authors.initials: G
authors.lastname: Klodowska-Duda
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Czyzewski
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Slawek
authors.forename: Monika
authors.initials: M
authors.lastname: Rudzinska
authors.forename: Maria
authors.initials: M
authors.lastname: Styczynska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opala
authors.forename: Marek
authors.initials: M
authors.lastname: Drozdzik
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Canter
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
authors.forename: Cezary
authors.initials: C
authors.lastname: Zekanowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010085:Oxidative Phosphorylation; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017382:Reactive Oxygen Species; D012306:Risk; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species