Objective: To analyze the influence of mitochondrial DNA (mtDNA) haplogroups on serum levels of molecular biomarkers in patients with osteoarthritis (OA).
Methods: We analyzed serum levels of molecular biomarkers of cartilage metabolism (collagen type-II markers: Coll2-1, Coll2-1NO2, C2C, CPII), synovial metabolism (hyaluronic acid (HA)) and cartilage and synovial turnover (YKL-40) in 73 OA cases and 77 healthy controls using enzyme-linked immunosorbent assays (ELISAs). All subjects 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 radiologic Kellgren/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 radiologic K/L grade in the serum levels of molecular markers were also found.
Conclusion A new role for mtDNA haplogroups emerges from this work. Our 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.