The impact of HFE genotypes and iron loading on joint disease: evidence for HFE-associated arthropathy without genetic haemochromatosis

Kiely, PDW; Farisogullari, B; Finzel, S; Carroll, GJ; McCarthy, G; Stack, J; Parisi, S; Porto, G; Richette, P; Nagy, G; Weidl, M; Rosenthal, A; Guggenbuhl, P; Banaszkiewicz, KJ; Engelhardt, S; Shearman, JD; Mitchell, D; Butzeck, B; Don, H; Barker, J; Brueton, V; Coathup, P; Dowsett, J; Duncan, M; Dunleavy, T; Fish, I; Hoggarth, A; McKinnon, M; Minter, J; Osborne, T; Smith, M; Wright, C; Machado, PM

doi:10.1016/j.ard.2026.10.3166

Gout & crystal arthritis

The impact of HFE genotypes and iron loading on joint disease: evidence for HFE-associated arthropathy without genetic haemochromatosis

Ann Rheum DisPublished 2 Nov 2026inception cohorts

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Authors' conclusion

A substantial proportion of individuals without haemochromatosis but carrying HFE genotypes fulfil EULAR HA-CC, without an association with ferritin levels or transferrin saturation. This supports a potential iron-independent contribution of HFE variants to arthropathy. Although 'haemochromatosis arthropathy' is found in people with genetic haemochromatosis, 'HFE associated arthropathy without genetic haemochromatosis' describes metacarpophalangeal and/or ankle joint disease with any HFE genotype.

Study context

Population: Participants from the EULAR haemochromatosis arthropathy (HA) inception cohorts; group 2 selected from rheumatology patients with persistent unexplained joint pain, potential HA, and/or pre-existing genotypingparticipants analysed from the EULAR HA inception cohorts
Participants: 373 participants

Comparison: Recognised HFE genotypes, with and without iron loading, vs osteoarthritis/calcium pyrophosphate arthropathy controls without iron overload
GROUP 1n = 154
GROUP 2An = 27
GROUP 2Bn = 72
GROUP 3n = 120
Outcome: HA-CC fulfilment

Methodological detailsbetween-group comparisons, genotype-stratified analyses, regression analyses

Between-group comparisons
Genotype-stratified analyses
Regression analyses

Main finding

As reported in the abstract

GROUP 171.4%

GROUP 2A22.2%

GROUP 2B43.1%

GROUP 36.7%

Further findings

Outcome	← Lower odds ←→ Higher odds →	Estimate	P value
Association of ferritin levels with HA-CC fulfilment (group 2)	0.512	OR 1.000 per 1 µg/L increase (95% CI 1.000–1.001)	P = 0.28
Association of transferrin saturation with HA-CC fulfilment (group 2)	0.512	OR 0.98 per 1% increase (95% CI 0.96–1.01)	P = 0.14
	0.512Odds ratio (log scale)

HA-CC fulfilment and 5 HA-CC features, group 2 vs group 3

Group 2 demonstrated significantly higher prevalence of HA-CC fulfilment and 5 HA-CC features than group 3, including participants with H63D variants

P < .003 all items

Reference

Authors: Kiely PDW, Farisogullari B, Finzel S, Carroll GJ, McCarthy G, Stack J, et al.
All 33 authors
Kiely PDW, Farisogullari B, Finzel S, Carroll GJ, McCarthy G, Stack J, Parisi S, Porto G, Richette P, Nagy G, Weidl M, Rosenthal A, Guggenbuhl P, Banaszkiewicz KJ, Engelhardt S, Shearman JD, Mitchell D, Butzeck B, Don H, Barker J, Brueton V, Coathup P, Dowsett J, Duncan M, Dunleavy T, Fish I, Hoggarth A, McKinnon M, Minter J, Osborne T, Smith M, Wright C, Machado PM
Journal: Annals of the Rheumatic Diseases
Published: 2 Nov 2026
DOI: 10.1016/j.ard.2026.10.3166
PubMed: 42971884

Topic: Gout & crystal arthritis

Group definitions

GROUP 1: C282Y homozygous with significant iron overload
GROUP 2A: C282Y homozygous without significant iron overload
GROUP 2B: other HFE genotypes irrespective of iron status

Key notes

P < .001 all comparisons

Original publication

The impact of HFE genotypes and iron loading on joint disease: evidence for HFE-associated arthropathy without genetic haemochromatosis. Ann Rheum Dis. Published 2 November 2026. doi:10.1016/j.ard.2026.10.3166

Read the original article ↗

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