title: mt4216C variant in linkage with the mtDNA TJ cluster may confer a susceptibility to mitochondrial dysfunction resulting in an increased risk of Parkinson's disease in the Irish.
abstract: Polymorphism of the mtDNA genome has been implicated as playing a role in the development and pathogenesis of Parkinson's disease (PD). A PCR-RFLP methodology was employed to generate genetic haplotypes for a cohort of 90 PD sufferers. No association was observed between the various mtDNA haplotypes observed and PD in comparison to healthy aged controls. The longevity-associated European J haplogroup and T haplogroup were identified and were both found to be in tight linkage with the mt4216C polymorphism. The mt4216C variant was observed at a significantly increased frequency in the PD cases (28%) in comparison to the healthy aged controls (15%; p=0.014). However, when the frequency of the mt4216C variant was examined in a cohort of 200 young controls (18-45 years) a similar frequency to the PD cases (25%) was observed. The frequencies obtained for the two branches of the J haplogroup (J1 and J2) and the T haplogroup in the cohort of PD subjects also reflected those observed for the young controls used in the previous longevity study. These findings lead one to postulate that the mt4216C variant, in linkage with the mtDNA TJ cluster, may influence mitochondrial dysfunction, resulting in an increased risk of PD.
authors.affiliation: Northern Ireland Regional Histocompatibility and Immunogenetics Laboratory, Blood Transfusion Building, City Hospital, Belfast BT9 7TS, Northern Ireland, UK. owenaross@hotmail.com
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Rose
authors.initials: R
authors.lastname: McCormack
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Maxwell
authors.forename: R Alistair
authors.initials: RA
authors.lastname: Duguid
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Quinn
authors.forename: Yvonne A
authors.initials: YA
authors.lastname: Barnett
authors.forename: I Maeve
authors.initials: IM
authors.lastname: Rea
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
authors.forename: J Mark
authors.initials: JM
authors.lastname: Gibson
authors.forename: Andrew
authors.initials: A
authors.lastname: Wallace
authors.forename: Derek
authors.initials: D
authors.lastname: Middleton
authors.forename: Martin D
authors.initials: MD
authors.lastname: Curran
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007494:Ireland; D008136:Longevity; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004272:DNA, Mitochondrial