Chondrocalcinosis and the haemochromatosis linked HFE C282Y homozygous variant in the UK Biobank

BackgroundC282Y genetic homozygosity is the main cause of the iron-overload disorder haemochromatosis. Musculoskeletal pain and arthropathy are common in haemochromatosis, but less is known about chondrocalcinosis (cartilage calcification) with the C282Y variant, especially in the community. We assessed knee chondrocalcinosis in iDXA (dual-energy X-ray absorptiometer) images from UK Biobank volunteers by HFE genotype. MethodsData were from 236 European genetic ancestry C282Y homozygotes and 236 age, sex, and BMI-matched controls with no C282Y alleles (48-80 years, mean 64.6, SD {+/-}7.6). 435 of 472 participants had relevant left and right knee iDXA imaging. Evidence of chondrocalcinosis was assessed by an experienced reporting radiographer blind to genotype to ensure unbiased and objective evaluation. Logistic regression models were age, sex and BMI matched. ResultsKnee chondrocalcinosis was present in 15.9% (14/88) of C282Y homozygous males and <5.9% (<5/84) of males without variants (OR=7.76, 95% CI: 1.71-35.25, p=0.008). 57.1% (8/14) of the male homozygotes with knee chondrocalcinosis reported knee pain during the previous three months, but <28.6% also had a haemochromatosis diagnosis. In females, 6.0% (8/134) of C282Y homozygotes had knee chondrocalcinosis, vs <3.9% (<5/129) without variants. However, the odds of chondrocalcinosis were not significantly higher in C282Y homozygotes (OR=1.98, 95% CI: 0.58-6.76, p=0.273), therefore a larger sample size may be required to detect a smaller effect in female homozygotes. ConclusionIn this community genotyped sample, male C282Y homozygotes had a markedly increased odds of knee chondrocalcinosis. Evaluation of serum ferritin levels to identify possible haemochromatosis may be justified in knee chondrocalcinosis management.