THU0413 MAJOR SUB-HAPLOGROUP H1 IS A RISK FACTOR FOR RAPIDLY PROGRESSIVE OSTEOARTHRITIS OF THE KNEE. DATA FROM THE OSTEOARTHRITIS INITIATIVE

Abstract

Background: There is a pressing need to identify individuals with accelerated osteoarthritis to include them in clinical trials and to implement prevention strategies. During the last years, the mtDNA haplogroups have been consistently associated with OA in terms of genetic factors influencing both the incidence and progression of the disease (1,2) Objectives: To analyze the influence of mtDNA haplogroups on the risk of rapid knee OA progression in patients from the Osteoarthritis Initiative (OAI). Methods: We selected Caucasian patients from the OAI that were assigned into three different groups based on previously described criteria: i) rapid progressors, with baseline KL grade 0-I in at least one knee and increase up to KL≥III during 48 month follow-up; ii) non-rapid progressors, with baseline KL grade 0-I in at least one knee and increase up to KL=II during 48 month follow-up; and iii) non-progressors, with KL grade 0-I at baseline in at least one knee and bilaterally stable during the 48-month follow-up period. We performed different regression models adjusting for the confounder clinical variables of gender, age, body mass index, contralateral OA, previous injury in target knee and total WOMAC. mtDNA haplogroups and major H sub-haplogroups (H1,H3,H5 and H*) were previously assigned using sequencing techniques. The analyses were performed using IBM SPSS Statistics v24 Results: We could assign the progression status to 2092 subjects, of which 181 were rapid progressors (8,7%), 321 non-rapid progressors (15,3%) and 1590 non-progressors (76%). All the classical risk factors for disease progression showed significant differences between rapid progressors and non-progressors, including gender (female) (OR=1,934; 95%CI:1,377–2,717;p After re-categorizing the dependent variable into rapid-progressors and non-rapid progressors, in addition to the significant association of the classical risk factors such as gender (female), age, BMI, contralateral OA, previous injury of target knee and total WOMAC at baseline, the sub-haplogroup H1 appeared significantly associated as a risk factor for rapid progression too (OR=1,781;95%CI:1,08 –2,919;p=0,022) Conclusion: The mtDNA haplogroups, more specifically the major sub-haplogroup H1, increase the risk of rapidly progressive OA of the knee. The assignment of this mitochondrial genetic sub-haplogroup could be useful as complementary genetic biomarker for the early identification of this OA phenotype