BACKGROUND: Multiple sclerosis (MS) is a debilitating disease of the central nervous system for which no definitive therapy has yet been developed. The etiology remains uncertain, but there is evidence of genetic susceptibility to the disease, including contributions from mitochondrial DNA (mtDNA) variations to the pathogenesis of MS. G15257A and G15812A are variations of the mtDNA tRNA(Thr) gene in MS sufferers of different populations. The present study tested the hypothesis of an association of the G15257A and G15812A variations of the mtDNA tRNA(Thr) gene to the susceptibility to MS in an Iranian population.

MATERIAL AND METHODS: Two hundred subjects included 100 MS patients and 100 unrelated healthy controls. DNA was extracted from blood samples by means of a salting-out method. The mtDNA fragment was amplified by polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) analysis was done by digestion of the PCR products with Acc I and Rsa I restriction endonuclease enzymes for mtDNA G15257A and G15812A variations, respectively. Afterwards, the restriction products were visualized by electrophoresis using 3% Agarose gel and safe DNA gel staining. To confirm the accuracy of genotyping procedure, sequencing of the mtDNA fragments was carried out in randomly selected samples.

RESULTS: The mtDNA G15257A variation was found in one of the 100 patients and one of the 100 controls (P=0.637) (odds ratio [OR]=1, 95% confidence interval [95% CI]=0.0-79.2). The mtDNA G15812A variation was not found in any of the 100 patients or 100 controls (0%) (P=1) (OR=1, 95% CI=0.0-79.2).

CONCLUSION: The evidence from the present study is inconsistent with the hypothesis that the G15257A and G15812A variations in the mtDNA tRNA(Thr) gene are associated with susceptibility to MS in the selected population.