Date: Monday, October 22, 2018
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Hand osteoarthritis (OA) can be a painful, disabling condition, with an increased prevalence in women, the elderly, and has a strong genetic component (hereditability index= 60%). Mitochondrial DNA haplotypes (mDNA haplotypes) track maternal genetic inheritance and have been used in understanding population genetics. Recently mDNA haplotypes have been associated with knee OA in the OAI and CHECK cohorts. Basic science studies of mDNA haplotypes have demonstrated that mDNA haplotypes modulate critical cell functions including ATP production, oxygen consumption, generation of oxidative species, mitochondrial and nuclear gene expression which impact bioenergetics, inflammatory responses, apoptosis, aging-related responses, and calcium metabolism. We explored, given the strong gender and genetic associations with Hand OA, whether mDNA haplotypes were associated with prevalent hand OA, symptomatic hand OA, thumb-base OA, symptomatic thumb OA in cross-sectional analyses, and incident hand OA, symptomatic hand OA, thumb-base OA, symptomatic thumb-base OA and hand OA progression in prospective analyses.
Methods: 3558 Caucasian participants in the Osteoarhtritis Initiative (OAI) had hand xrays in the dominant hand read for radiographic severity (Kellgren-Lawrence [KL] grade) at baseline and year 4, and had mDNA haplotypes assessed at baseline. Eleven mDNA haplotypes were categorized into 5 groups (H, UK, T, J, other) with 103 samples excluded due to technical and sampling errors. Age and sex adjusted odds ratios were calculated comparing all mDNA haplotypes to the H haplotypes. Hand OA was defined as two joints on different rays with KL≥2 excluding the thumb-base joints, thumb OA as KL≥2 in CMC or ST-T joints. Symptomatic hand OA was defined as either new interphalangeal joint (IPJ) OA at year 4 in a previous symptomatic individual, new symptoms in a participant with previous hand OA, or both new symptoms and meeting the hand OA definition. Hand OA progression was defined the mean change in number of joints with a new KL grade over the four-year period.
Results: For Incident disease, mDNA haplotypes of UK (OR=0.70, 95%CI 0.53,0.92) and T (OR=0.57, 95% CI 0.38,0.86) were associated with protective effects compared to H for symptomatic hand OA and symptomatic thumb-base OA of UK (OR=0.68, 95%CI 0.52,0.89) and T (OR=0.49, 95% CI 0.32,0.79). False Discovery Rate (FDR) p<0.05. Evaluating hand OA progression, the T group compared to the H group had a reduced mean rate of progression of -0.11, p<0.01. FDR p<0.08. No association was found for prevalent OA or incident radiographic hand or thumb OA.
Conclusion: In a sample of Caucasian participants in the OAI, the mDNA haplotype T and Uk appear to be inversely associated with incident symptomatic hand and thumb OA and T with hand OA progression. This differs from the findings of an inverse association with knee OA incidence and progression with mDNA haplotype J compared to H previously reported in this same OAI sample. Given multiple comparisons, caution should be used in interpreting our results and our findings need to be replicated in other cohorts.
To cite this abstract in AMA style:Eaton C, Roberts M, Driban JB, Haugen IK, Schaefer LF, Lu B, Jackson RD, Hochberg MC, Kwoh CK, Blanco FJ, McAlindon TE. Association of Mitochondrial DNA Haplotypes with Symptomatic Hand and Thumb Based Osteoarthritis and Hand OA Progression [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/association-of-mitochondrial-dna-haplotypes-with-symptomatic-hand-and-thumb-based-osteoarthritis-and-hand-oa-progression/. Accessed August 14, 2020.
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