Haemochromatosis HFE genotypes and association with chondrocalcinosis: Early data from analysis in UK Biobank

Abstract

The iron-overload disorder haemochromatosis is primarily caused by the homozygous HFE p.C282Y variant. Musculoskeletal changes including arthropathy and chondrocalcinosis (cartilage calcification) are well-recognised features of the clinical disease, however, less is known about chondrocalcinosis formation in those with the p.C282Y variant. We used UK Biobank iDXA (dual-energy X-ray absorptiometer) images to assess for chondrocalcinosis in the knee and to explore any association with p.C282Y genotype.

Methods: We used data from 144 p.C282Y homozygotes of European genetic ancestry (aged 48 to 80years) and 144 controls matched for age, sex, and BMI. Within these 288 participants, 264 had relevant knee iDXA (GELunar, Bedford) imaging. These images were reviewed for radiological evidence of chondrocalcinosis by an experienced reporting radiographer. Logistic regression models assessed associations between the p.C282Y homozygous genotype and chondrocalcinosis. Analyses were stratified by sex and adjusted for age.

Results: Male p.C282Y homozygotes had significantly increased odds of radiological chondrocalcinosis in either imaged knee when compared with matched controls without HFE haemochromatosis mutations (OR=12.59 [95% CI:1.51-104.70] p=0.019). Female p.C282Y homozygotes did not have increased odds of chondrocalcinosis in either knee, (OR=3.51 [95% CI:0.69-17.79] p=0.129). Larger sample sizes are needed to increase power and we plan to review further iDXA images within UK Biobank and also to explore any associations with an arthritis diagnosis.

Conclusion: In this community genotyped sample, male p.C282Y homozygotes demonstrated significantly increased odds of developing chondrocalcinosis within the knee. These results may support further investigations such as serum ferritin levels when chondrocalcinosis is identified on imaging.