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A Mitochondrial Etiology of Neurodegenerative Diseases: Evidence from Parkinson's Disease
Author(s) -
Khusnutdinova Elza,
Gilyazova Irina,
RuizPesini Eduardo,
Derbeneva Olga,
Khusainova Rita,
Khidiyatova Irina,
Magzhanov Rim,
Wallace Douglas C.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1427.001
Subject(s) - haplogroup , mitochondrial dna , genetics , human mitochondrial dna haplogroup , biology , disease , haplotype , allele , gene , medicine , pathology
Evidence continues to accrue implicating mitochondrial dysfunction in the etiology of a number of neurodegenerative diseases. For example, Parkinson's disease (PD) can be induced by mitochondrial toxins, and nuclear DNA (nDNA) loci linked to PD have been associated with mitochondrial dysfunction. Although conclusions about the role of mitochondrial DNA (mtDNA) variants in PD vary, we argue here that this is attributable to the novel genetics of the mtDNA and the fact that clinically relevant mtDNA variation encompasses ancient adaptive polymorphisms, recent deleterious mutations, and somatic mutations. An mtDNA association with PD is supported by an analysis of the Russian Tatar population which revealed that polymorphisms associated with haplogroup H mtDNAs increased PD risk (odds ratio [OR]= 2.58, P = 0.0001), whereas those associated with haplogroup UK cluster mtDNAs were protective (OR = 0.38, P = 0.003). Moreover, mtDNA sequencing revealed that PD patients with either haplogroup H or UK cluster mtDNAs can harbor additional recent variants that might further modulate PD risk. Therefore, the complexity of PD genetics may reflect the complex mitochondrial genetics.