Mitochondrial haplogroups in patients with rheumatoid arthritis with respect to biological treatment

Background/Purpose: Throughout evolution mutations in mitochondrial DNA (mtDNA) have accumulated sequentially subdividing the human population into different haplogroups classificed from A-Z. Specific mtDNA haplogroups have been associated with the development of several conditions such as Alzheimer and Parkinsons diseases. RA is a chronic auto-inflammatory disorder in which the pathogenesis is not fully understood. We analyzed the distribution of mtDNA haplogroups in a cohort of patients with RA defined by disease activity, presence of rheumatoid factor, and biological or conventional treatment. We compared the distribution of mtDNA haplogroups in the RA-cohort with two historical control groups from the background population. Methods: Two-hundred nineteen consecutive patients with RA had mtDNA, isolated, sequenced and haplogroups were identified from blood samples. Patients were diagnosed according to the American College of Rheumatology (ACR)/European league against Rheumatism (EULAR) criteria. Demographic and clinical data (rheumatoid factor status, erosions, disease activity score 28-joints (DAS-28), biological/synthetic anti-rheumatic treatments were retrieved from the Danish nationwide database (DANBIO). Logistic regression analyses were performed to test for associations. Results: One-hundred eighty-four patients were eligible for analysis (29 were excluded due to rare non-European haplogroups, 6 had unknown haplogroups). Haplogroup frequencies were as follows: H (n= 88, 47.8%), U (n= 37, 20.1%), T (n= 22, 12.0%), J (n= 16, 8.7%), K (n= 11, 5.9%), HV (n= 6, 3.3%) and V (n= 4, 2.2%). In the overall RA-cohort the distribution of individual haplotypes was identical to the background population. None of the haplogroups were significantly associated with gender, anti-CCP, IgM RF or DAS-28. Macrohaplogroup HV was associated with administration of biological treatment (OR = 2.13; 95% Confidence Interval (CI): 1.13 - 4.07; p = 0.020). However, we found a trend towards fewer erosions in patients with haplogroup HV (OR = 0.54, 95% CI: 0.29 - 1.00, p = 0.051). Conclusion: The distribution of mtDNA haplogroups in the RA-cohort did not differ from the background population. However, there was a significant overrepresentation of individuals with haplogroup HV (OR 2.13) among patients undergoing biological treatment. When patients were grouped according to presence of radiographic erosion there was a trend pointing in the opposite direction. Erosive patients were less likely to belong to haplogroup HV (OR 0.54). When subjects were stratified according to DAS-28 level there were no significant associations with a certain haplogroup. We have shown that in a randomly selected cohort of patients with RA the HV mtDNA haplogroup may be overrepresented in a subgroup of patients, but no clear association with respect to diseases severity was observed.