Mitochondrial DNA haplogroups modulate the serum levels of biomarkers in patients with osteoarthritis.
OBJECTIVE
To analyse the influence of mitochondrial DNA (mtDNA) haplogroups on serum levels of molecular biomarkers in patients with osteoarthritis (OA).


METHODS
Serum levels of molecular biomarkers of cartilage metabolism (collagen type II markers: C-terminal neoepitope generated by the collagenase-mediated cleavage of collagen type II triple helix (C2C), collagen type II (Coll2-1, and its nitrated form, Coll2-1NO(2)), procollagen type II (CPII)), synovial metabolism (hyaluronic acid (HA)) and cartilage and synovial turnover (cartilage glycoprotein 39 (YKL-40)) were analysed in 73 patients with OA and 77 healthy controls using ELISAs. All participants had been previously genotyped for the mtDNA haplogroups J, U and H. Non-parametric and multivariate analysis were performed to test the effects of the clinical variables, including gender, age, smoking status, diagnosis, mtDNA haplogroups and radiological Kellgren and Lawrence (K/L) grade on the serum levels of the molecular markers.


RESULTS
Non-parametric analysis found increased serum levels of HA in patients with OA, while the values for C2C and the C2C/CPII ratio were significantly higher in the healthy controls. A multiple regression analysis showed a relationship between the mtDNA haplogroups and serum levels of the typical collagen type II markers. Carriers of the mtDNA haplogroup H had higher levels while carriers of the mtDNA haplogroup J showed lower levels. Statistically significant interactions between mtDNA haplogroups and diagnosis and between mtDNA haplogroups and radiological K/L grade in the serum levels of molecular markers were also found.


CONCLUSIONS
A new role for mtDNA haplogroups emerges from this work. The results suggest that the mtDNA haplogroups interact significantly with the serum levels of OA-related molecular markers, suggesting the possibility of their use as a complementary assay with these molecular markers.
Rego-Pérez
I
I
Osteoarticular and Aging Research Laboratory, Rheumatology Division, Complejo Hospitalario Universitario A Coruña, 15006-A Coruña, Spain.
Fernández-Moreno
M
M
Deberg
M
M
Pértega
S
S
Fenández-López
C
C
Oreiro
N
N
Henrotin
Y
Y
Blanco
F J
FJ
D000368:Aged; D015415:Biomarkers / Q000097:blood; D024043:Collagen Type II / Q000097:blood; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D010446:Peptide Fragments / Q000097:blood; D011859:Radiography; D012189:Retrospective Studies; D012720:Severity of Illness Index
D015415:Biomarkers; D024043:Collagen Type II; D004272:DNA, Mitochondrial; D010446:Peptide Fragments; C510280:collagen type II (108-116); C510281:collagen type II (108-116), (NO2)Tyr(111)-; D006820:Hyaluronic Acid