Large scale screening of the mitochondrial DNA reveals no pathogenic mutations but a haplotype associated with multiple sclerosis in Caucasians

We report the first large-scale screening of mitochondrial (mt) DNA in 77 C aucasian patients with relapsing-remitting or secondary progressive form of multiple sclerosis (MS) and in 84 Caucasian controls by using the method o f restriction site polymorphism and haplotype analysis. No pathogenic mtDNA mutation was found in association with MS. However, mtDNA haplotypes K* an d J* defined by the simultaneous presence of DdeI restriction sites at nucl eotides 10,394 and 14,798 of the mtDNA in haplogroups K and J showed associ ation with MS at a P-value of 0.001. A relative increase of MS patients com pared to controls either with the J* or with the K* haplotype (+10,394DdeI/ + 14,798DdeI in haplogroup J or K) also was detected (each with a P<0.05). No distinct phenotypic characteristics of MS were-observed when clinical da ta of patients with haplotypes K* or J* were analyzed. In addition to previ ous complete sequencing in several MS patients, the population screening of mtDNA presented here suggests that mtDNA point mutations are not likely to be involved in the pathogenesis of typical forms of MS. However, the mitoc hondrial genetic background (haplotype K* and J*) may moderately contribute to MS susceptibility. The reported association between MS and Leber's here ditary optic nerve atrophy, a disease caused by mtDNA point mutations prefe rentially occurring in haplogroup J, may be at least in part related to the overlapping mitochondrial genetic background of the two diseases.