Mitochondrial genome and risk of multiple sclerosis

Abstract

Mitochondrial DNA (mtDNA) polymorphism makes a certain contribution to the formation of a genetic risk of multiple sclerosis (MS).Objective: to analyze the frequency of mtDNA variants in patients with MS and control individuals in the Russian population. A similar study was conducted for the first time.Patients and methods. The polymorphism of mtDNA was studied in the Russian population: in 283 unrelated patients with relapsing-remitting MS and in 290 unrelated healthy controls matched for gender and age.Results and discussion. The frequency of haplogroup J in the patients with MS was twice higher than that in the control group (p=0.0055) (odds ratio (OR) 2.00; 95% confidence interval (CI). 1.21–3.41). This association was mostly observed in women (p=0.0083) (OR 2.20; 95% CI, 1.19–4.03). There was also a significant association of the A allele of MT-ND5 (m. 13708G>A) with MS (p=0.03) (OR 1.89; 95% CI 1.11–3.32). Sex stratification showed that the association with MS was significant only in women (p=0.009; OR, 2.52; 95% CI, 1.29–5.14). Further investigations will aim to analyze mtDNA variability (at the level of individual polymorphisms, haplogroups, and whole genome) in patients with relapsing-remitting MS and in those with primary progressive MS versus healthy individuals and patients with relapsing-remitting MS according to disease severity.Conclusion. The data obtained in the Russian population suggest that mtDNA variations are involved in MS risk, to a greater extent in women.

Mitochondrial DNA haplogroup analysis in Saudi Arab patients with multiple sclerosis

“…Caucasians [42] and a significant association with MS in Russian [27,28], Persian [29] and Bulgarian [30] patients. Results from this study also revealed the presence of haplogroup T in MS patients only.…”

“…We also did not observe a significant difference in the frequency of haplogroup J between patients and controls. An earlier study by Reynier et al, [ 43 ] found haplogroup J only in MS patients with optic neuritis (ON) but not in MS patients without visual symptoms, and suggested that this haplogroup might constitute a risk factor for ON occurrence when it is coincidentally associated with MS, but not as a risk factor for developing MS. On the other hand, other studies have revealed a moderate effect of haplogroup J with MS susceptibility in Caucasians [ 42 ] and a significant association with MS in Russian [ 27 , 28 ], Persian [ 29 ] and Bulgarian [ 30 ] patients. Results from this study also revealed the presence of haplogroup T in MS patients only.…”

“…Recent studies have reported that mtDNA background affects the expression of human disease such as PD and AD [24,25]. MS has also been reported to be modulated by mtDNA haplogroups [26][27][28][29][30][31]. Most of these reports have shown population specific associations of diseases with particular haplogroups.…”

“…In MS, some studies showed an association of haplogroup U in Caucasians [ 26 ] but not in a Russian patients [ 27 ]. Studies also reported a consistent association of haplogroup J with the risk of MS in Russian [ 27 , 28 ], Persian [ 29 ] and Bulgarian [ 30 ] patients, while others failed to find any association of haplogroup J with MS in Basque patients [ 31 ].…”