Background Significant influence of the mtDNA haplogroups on radiographic progression of knee OA (KOA) has been reported; however, further validation in other well-defined prospective cohorts is necessary
Objectives To validate, in patients from the CHECK cohort, the results obtained in patients from the OAI by which the mtDNA haplogroups influence the radiographic progression of knee Osteoarthritis. The CHECK cohort is a running 10-year prospective multi-center cohort of subjects, with pain and/or stiffness of one and/or both knees
Methods We assigned the mtDNA haplogroups to the entire CHECK cohort (n=1002 subjects). In accordance with the early-stage OA in CHECK subjects (van Spil et al 2012), we selected subjects that did show radiographic KOA at baseline (K&L grade=1 for the left and/or right knee), reaching a total of n=417 subjects. Progression in these subjects was defined as an increase of ≥1 K&L grade for the left and/or right knee during 5 years follow-up period.Appropriate statistical analyses, including Receiver Operating Curves (ROC) with their respective Area Under the Curve (AUC), were carried out using SPSS software (v.19)
Results The 417 subjects that met the eligibility criteria to study radiographic progression included 81.1% females and 18.9% males, they were older than 45 years (mean age: 56.24±5.07 years; range: 45-66) and had a mean BMI of 26.80 kg/m2 (range: 15.43-48.85). Chi-square analysis revealed that the mtDNA haplogroup T significantly associated with lower risk of radiographic progression (OR=0.467; CI=0.250-0.874; p=0.015); analysing by mtDNA clusters, the cluster TJ significantly associated with lower risk of progression too (OR=0.586; CI=0.366-0.939; p=0.025). By comparing each of the mtDNA haplogroups with the most common haplogroup H in the regression model, we detected that carriers of the mtDNA haplogroup T were at lower risk for K&L grade progression (31.4% progressors) than carriers of the most common mtDNA haplogroup H (50.6% progressors) (OR=0.414; CI=0.204-0.844; p=0.015); in terms of mtDNA clusters, subjects in cluster TJ were at lower risk of progression than subjects in the cluster HV (OR=0.551; CI=0.317-0.955; p=0.034). Additionally, either including mtDNA haplogroups or mtDNA clusters in the regression model, both BMI (OR=1.064; CI=1.010-1.120; p=0.020) and bilateral KL=1 at baseline (OR=3.595; CI=2.345-5.510; p<0.001) were also significantly associated with an increased risk of radiographic progression of KOA attending to K&L grade. The AUC of this regression model was 0.723 and 0.722 after including either haplogroups or clusters respectively.
Conclusions As noted in KOA patients of the OAI cohort, the early identification and classification of patients with haplogroup T and the most common haplogroup H would permit to identify those patients more prone to a rapid radiographic progression of the disease
Van Spil WE, et al. Cros-sectional and predictive associations between plasma adipokines and radiographic signs of early-stage knee osteoarthritis: data from CHECK. Osteoarthritis Cartilage 2012;20:1278-1285
Acknowledgements We would like to thank the participants, principal investigators, coinvestigators and staff of the CHECK study.
Disclosure of Interest None declared