Mitochondrial variations unlikely cause of osteoarthritis

By Lynda Williams, Senior medwireNews Reporter

Researchers have been unable to confirm a link between the development of osteoarthritis (OA) and maternally inherited mitochondrial DNA (mtDNA) variants.

The study, published in the Annals of Rheumatic Diseases, compared 138 mtDNA single nucleotide polymorphisms (SNPs) for 7393 patients with OA participating in the arcOGEN consortium and 5122 controls registered in the Wellcome Trust Case Control consortium 2 study.

After excluding 90 SNPs from the analysis due to missing data or other quality control concerns, the researchers failed to find a significant association between OA and any of the remaining 48 SNPs.

Nor was an association discovered after adjusting for gender, knee or hip OA site, and whether OA was diagnosed by radiograph or arthroplasty.

Their findings are in contrast to two earlier-reported studies indicating a decreased risk for knee OA for mtDNA haplogroups J and JT, and a reduced risk for hip OA with haplogroups J and J1c.

However, these studies were small and underpowered statistically, and conducted in a different geographic population, the team notes. Furthermore, the studies reported different haplogroup associations for different joints and different genders.

Research has suggested that mitochondrial dysfunction may contribute to the development of OA by interrupting respiratory chain activity in chondrocytes, and disrupting function by increasing reactive oxygen species production.

However, there is yet no known mechanism for how mtDNA could influence joint-specific disease, the researchers say.

"The evidence linking OA to mtDNA is not compelling at present," comment John Loughlin (Newcastle University, UK) and co-authors of the current study.

They conclude: "If an association does exist between OA and mtDNA, it is likely that this will only be resolved through extensive genotyping, ideally at the whole mtDNA level, in a much larger cohort of cases and controls and should be consistent in more than one geographic region."

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