title: Mitochondrial DNA T4216C and A4917G variations in multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) affects the brain and spinal cord and long has been the topic of global research; yet there is no commonly accepted cause and no cure for the disease. Mounting evidence supports the role of genetics in susceptibility to MS. From this perspective, a current effort focuses on the neurogenetics of the complex pathogenesis of MS in relation to factors such as mitochondrial DNA (mtDNA) variations. T4216C and A4917G are common mitochondrial gene variations associated with MS. The present study tested whether mtDNA T4216C variation in the NADH Dehydrogenase 1 (ND1) mtDNA gene and A4917G variation in the mtDNA NADH Dehydrogenase 2 (ND2) gene are associated with MS in an Iranian population.
  
  
  METHODS
  Blood samples were collected from 100 patients with MS and 100 unrelated healthy controls, and DNA extraction was performed by salting-out. By means of appropriate primers, polymerase chain reaction (PCR) amplification was carried out for the mtDNA fragment. Afterwards, the PCR products were digested using Nla III and Acc I restriction endonuclease enzymes for analysis of Restriction Fragment Length polymorphism (RFLP) in mtDNA T4216C and A4917G variations, respectively. With electrophoresis by means of 3% agarose gel and safe DNA gel stain, we imaged restriction products in a UV transilluminator. The accuracy of genotyping procedure was confirmed by sequencing the mtDNA fragment.
  
  
  RESULTS
  No significant statistical difference in the frequency of the T4216C mtDNA variation was found between the patients (24%) and the control subjects (21%) (P=0.61). Logistic regression analysis showed an OR of 1.1 (95% CI=0.5-2.4). Moreover, there was no significant statistical difference in the frequency of mtDNA A4917G variation between the cases (11%) and the controls (9%) (P=0.637). Logistic regression analysis revealed an odds ratio (OR) of 1.2 with 95% CI of 0.4-3.5.
  
  
  CONCLUSIONS
  The present study revealed no association between MS and T4216C variation in the ND1 mtDNA gene and A4917G variation in the mtDNA ND2 gene in the Iranian population.
authors.affiliation: Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Sasan
authors.initials: S
authors.lastname: Andalib
authors.affiliation: Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: talebi511@yahoo.com.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Talebi
authors.affiliation: Division of Regenerative Medicine, School of Medicine, Faculty of Medical and Human Sciences, The University of Manchester, UK; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: esakhinia@yahoo.co.uk.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Sakhinia
authors.affiliation: Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Farhoudi
authors.affiliation: Department of Public Health Sciences, Karolinska Institute, Stockholm, Sweden; Trauma Epidemiology and Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Homayoun
authors.initials: H
authors.lastname: Sadeghi-Bazargani
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007492:Iran; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; C088908:NADH dehydrogenase II; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I
keywords: A4917G; MS; Mitochondrial DNA; Multiple sclerosis; T4216C; mtDNA variation