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The H63D variant in the HFE gene predisposes to arthralgia, chondrocalcinosis and osteoarthritis.

Alizadeh BZ, Njajou OT, Hazes JM, Hofman A, Slagboom PE, Pols HA, van Duijn CM

Department of Epidemiology & Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands.

OBJECTIVES: To investigate the relation between the HFE C282Y and H63D variants with arthralgia and joint pathology in the population-based Rotterdam Study. METHODS: From a cohort of 7983 people aged 55 years and over, 2095 randomly drawn subjects were genotyped for C282Y and H63D variants. We compared the frequency of arthralgia, and the presence of chondrocalcinosis, osteophytes, joint space narrowing and radiographic osteoarthritis in hand, hip and knee joints, and Heberden's nodes in carriers of HFE variants with that in non-carriers. RESULTS: Overall, there was a significantly higher frequency of arthralgia (odds ratio 1.6; 95% CI 1.0 to 2.6), oligoarthralgia (2.3; 1.2 to 4.4) and Heberden's nodes (2.0; 1.1 to 3.8) in H63D homozygotes compared with non-carriers. In subjects aged 65 years or younger, H63D homozygotes had significantly more often polyarthralgia (3.1; 1.3 to 7.4), chondrocalcinosis in hip or knee joints (4.7; 1.2 to 18.5), and more hand joints with osteophytes (6.1+/-1.0 vs 4.4+/-0.3), space narrowing (2.8+/-0.5 vs 1.0+/-0.1), radiographic osteoarthritis (4.4+/-0.7 vs 2.0+/-0.2) and Heberden's nodes (3.1; 1.3 to 12.8) than non-carriers. We found no relation of arthralgia or joint pathology to C282Y, but compound heterozygotes had a significantly higher frequency of arthralgia (2.9; 1.0 to 9.3), chondrocalcinosis in hip joints (6.5; 1.8 to 22.3), and an increased number of osteophytes in knee (6.9+/-1.2, n = 5 vs 2.4+/-0.1) joints at a later age (>65 years). CONCLUSIONS: The HFE H63D variant may explain, at least in part, the prevalence of arthralgia in multiple joints sites, chondrocalcinosis, and hand osteoarthritis in the general population.

Published 15 October 2007 in Ann Rheum Dis, 66(11): 1436-42.
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