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.