A Mitochondrial Etiology of Neurodegenerative Diseases: Evidence from Parkinson's Disease Export

@article{citeulike:3780198, abstract = {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.}, author = {Khusnutdinova, Elza and Gilyazova, Irina and Ruiz-Pesini, Eduardo and Derbeneva, Olga and Khusainova, Rita and Khidiyatova, Irina and Magzhanov, Rim and Wallace, Douglas C.}, citeulike-article-id = {3780198}, citeulike-linkout-0 = {http://dx.doi.org/10.1196/annals.1427.001}, citeulike-linkout-1 = {http://www.ingentaconnect.com/content/bsc/nyas/2008/00001147/00000001/art00002}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19076426}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19076426}, doi = {10.1196/annals.1427.001}, issn = {0077-8923}, journal = {Annals of the New York Academy of Sciences}, keywords = {disease, evolution, genetic, human, interest, litrev, medicine, mitochondria, mtdna, variant}, number = {1}, pages = {1--20}, posted-at = {2009-01-19 16:12:30}, priority = {0}, publisher = {Blackwell Publishing}, title = {A Mitochondrial Etiology of Neurodegenerative Diseases: Evidence from Parkinson's Disease}, url = {http://dx.doi.org/10.1196/annals.1427.001}, volume = {1147} }

TY - JOUR ID - citeulike:3780198 L3 - citeulike-article-id:3780198 N2 - 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. IS - 1 JF - Annals of the New York Academy of Sciences SN - 0077-8923 EP - 20 TI - A Mitochondrial Etiology of Neurodegenerative Diseases: Evidence from Parkinson's Disease PB - Blackwell Publishing VL - 1147 SP - 1 KW - disease KW - evolution KW - genetic KW - human KW - interest KW - litrev KW - medicine KW - mitochondria KW - mtdna KW - variant AU - Khusnutdinova, Elza AU - Gilyazova, Irina AU - Ruiz-Pesini, Eduardo AU - Derbeneva, Olga AU - Khusainova, Rita AU - Khidiyatova, Irina AU - Magzhanov, Rim AU - Wallace, Douglas UR - http://dx.doi.org/10.1196/annals.1427.001 ER -