Mitochondrial DNA variants in Bulgarian patients affected by multiple sclerosis

Abstract

The occurrence of multiple sclerosis (MS) in subjects clustering to a particular mitochondrial DNA (mtDNA) haplogroup/haplotype or carrying mtDNA mutations associated with Leber's hereditary optic neuropathy (LHON) has suggested that mitochondrial genome may contribute to susceptibility to MS. In the present study, 58 unrelated Bulgarian patients with relapsing remitting form of MS and 104 randomly selected healthy individuals were analysed for the presence of 14 mtDNA polymorphisms determining major European haplogroups as well as three (4216, 14 798, 13 708) secondary LHON mutations. Restriction enzyme analysis used to screen patients and controls for the common haplogroup-associated polymorphisms showed that each of these changes was present in MS patients at a similar frequency to control subjects. However, 21 of the 58 patients (36.2%) were positive for T4 216C mutation, while only 11.3% of the controls carried this secondary LHON base change (P < 0.01; OR = 4.38). Our finding indicated that 4216C base substitution could be considered as a predisposing marker for MS and supported the hypothesis that particular mtDNA variants could contribute to genetic susceptibility of MS, and merits further investigation.

Investigation of the Role of Mitochondrial DNA in Multiple Sclerosis Susceptibility

“…Our results differ to those reported in a recent study in Bulgarian multiple sclerosis patients which showed evidence for an association with the secondary LHON mutation 4216C [19]. In the present study the 4216C allele was present in 24.3% and 27.2% of cases and controls respectively (p = 0.5256), the observed trend being in the opposite direction to that identified in the Bulgarian study [19].…”

“…The data regarding haplogroups have been somewhat contradictory with some researchers suggesting that haplogroups K and J increase risk [17], [21] while others have found evidence that haplogroup J/T is protective [18]. The possible relevance of LHON related mutations has understandably received attention and a suggestion that secondary LHON mutations (mutations which are more common in LHON but are not directly pathogenic for the condition) increase the risk of multiple sclerosis has been suggested [9], [13], [19], [22] whilst another study showed a decreased risk [13].…”

Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression

“…Although there are reports of mitochondrial DNA polymorphisms in particular individuals and subgroups of MS patients (42, 43), it is considered unlikely that mitochondrial DNA mutations are widely associated with typical forms of MS (44). However, a relationship between MS disease progression and acquired mitochondrial dysfunction secondary to inflammation-induced damage to the mitochondrion has been hypothesized (5).…”

Mitochondrial Mutation in Iranian Patients with Multiple Sclerosis, Correlation Between Haplogroups H, A and Clinical Manifestations

“…Vanopdenbosch et al (2000) showed that the association of LHON and MS is more than a coincidence. Mihailva, showed that mutation of T4 216C may be predisposing marker for MS (Mihailova et al 2007). In our study, the most prevalent mutations were J, L, and T. This result is the same as another report from Iranian patients , and these haplogroups may be a predisposing factor for MS in Iranian patients.…”