title: Association of the mt-ND2 5178A/C polymorphism with Parkinson's disease.
abstract: Mitochondria play an important role in the etiology of Parkinson's disease (PD). While mutations in the mitochondrial DNA (mtDNA) have been shown to accumulate in PD, no specific mtDNA polymorphisms have been associated with susceptibility or resistance to PD. A cytosine to adenine transversion at base pair 5178 in the mtDNA has been associated with increased longevity and resistance against a number of age related disorders and has been shown to decrease mitochondrial reactive oxygen species (ROS) production. We sought to determine whether 5178A is associated with resistance against PD in a Han Chinese population. To assess its association with PD, we genotyped 484 idiopathic PD patients and 710 control individuals for 5178C/A. Genotyping was performed using restriction fragment length polymorphism (RFLP) analysis. There was no significant association between 5178A and PD (P=0.308) when analyzing the entire population. However, sub-group analysis revealed that in males the frequency of 5178A was significantly lower in PD patients (27.7% in controls vs 20.0% in PD patients, P=0.027). Stratification of the population by age showed that this trend held across age groups but only reached statistical significance in males aged 60-70 (29.1% in controls vs 14.05 in PD patients, P=0.011). In conclusion, we demonstrated that the frequency of 5178A was significantly decreased in male PD patients in a Han Chinese population. This polymorphism may be associated with resistance against the development of PD when in combination with loci on the Y chromosome.
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197, Rui Jin Er Road, Shanghai 200025, China; Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Neurology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Gusdon
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197, Rui Jin Er Road, Shanghai 200025, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610-0275, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610-0275, USA.
authors.forename: Clayton E
authors.initials: CE
authors.lastname: Mathews
authors.affiliation: Clinical and Translational Science Institute (CTSI), University of Pittsburgh School of Medicine, Pittsburgh, PA15261, USA.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Charleen T
authors.initials: CT
authors.lastname: Chu
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197, Rui Jin Er Road, Shanghai 200025, China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Ding
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197, Rui Jin Er Road, Shanghai 200025, China. Electronic address: chen_sd@medmail.com.cn.
authors.forename: Sheng-di
authors.initials: SD
authors.lastname: Chen
mesh_terms: D000367:Age Factors; D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000235:genetics*; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012737:Sex Factors
chemical_list: D009245:NADH Dehydrogenase; C521326:NADH dehydrogenase subunit 2, human
keywords: 5178A; Complex I; Mitochondrial DNA; NADH dehydrogenase; Parkinson’s disease; mt-ND2