Multiple Sclerosis and Mitochondria

Multiple Sclerosis Disease and Mitochondria

Multiple Sclerosis (MS) is a multifocal demyelinating central nervous system disorder. To assess relationship between mtDNA haplogroups and MS, we have sequenced the mtDNA HVS-I in 54 MS patients and 100 control subjects. In this study, kinetic analysis of mitochondrial respiratory chain complex I enzyme was performed on intact mitochondria isolated from fresh skeletal muscle in MS patients (n =10) and control subjects (n =11). The frequencies of the Asian (M, BM) and European (N, J, K) mtDNA haplogroups in five major regions of Iran was investigated. Unexpectedly, the frequencies of the Asian haplogroups M and BM were low in Iran (2.34% for haplogroup M; 17.6% for haplogroup BM and 80.06% for haplogroup N).

We have found that haplogroups A and K are significantly more abundant in MS patients (P=0.042 for haplogroup A and P=0.0005 for haplogroup K). Our findings showed that complex I activities were significantly reduced ( P=0.007) in patients compared with control. However, we could not find deletion in mtDNA of patients with MS. Our results revealed that 15 (75%) out of 20 MS patients had point mutations. This study suggested that point mutation occurred in mtDNA might be involved in pathogenesis of MS. Our data suggest that Iranian tribes probably played a remarkable role in the formation of these ethnic groups. It gives the indication that the haplogroup J may be older than 6000-10000 years, and probably developed in Iran, and then expanded to different regions in Europe and Northwest Asia.

Of personal interest to me as an MS sufferer. Yet again, MtDNA shows itself to be non neutral.

3 responses to “Multiple Sclerosis and Mitochondria

  1. Thank you so much for posting this!

    I am from Haplogroup K and have been experiencing MS symptoms for 2 years. Testing to take place in a couple of months.

    el

  2. Yet again, MtDNA shows itself to be non neutral.

    But AFAIK all known harmful mutations are at the end of the mtDNA genealogical tree, in short terminal branches (they are “recent” mutations). Obviously, in the long run, such branches will tend to become extinct and that surely happened in the past too (that’s why we don’t find upstream harmful mutations). It is non-neutral at times but the bias effect is not so important in the long run, just that such branches are pre-tagged for extincton, while the others, that are not pre-tagged, may or may not become extinct.

    The occasional non-neutrality does not substantively affect the overall tree as seen from today because each haplogroup has terminal branches with both deletereous and neutral mutations and only the latter ones are likely to survive in the long run. It may have affected the viability of some aDNA clades that appear to have been more common in the past than today though.

    Another thing would be to find mDNA clades that include important adaptative mutations (maybe a more effective metabolism or whatever) but guess these must be rarer – because of the fact that it’s a lot easier to produce an harmful or even fatal error randomly than an improvement.

  3. The point is more that MtDNA seems to have ‘function’, making it subject to selection. I think one of the studies I’ve got around shows L haplotypes don’t fare as well in colder climates.

    I’ve seen too many studies now showing it’s subject to selection for different reasons. You should take a look at what John Hawkes (blogroll) has to say on the subject. He’s pretty much come to the conclusion that the lack of N MtDNA is meaningless too.

    A related issue is the lack of anomalous Mt DNA in South America. They’ve found Australoid remains all over the place, but no MtDNA or Y DNA that could have come from them. They were definitely modern humans, genetic trace. It supports the possiblity N DNA was just ‘lost’.

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