HFE C282Y homozygosity is associated with an increased risk of total hip replacement for osteoarthritis.
OBJECTIVE
The evidence for an association between mutations in the HFE (hemochromatosis) gene and the risk of hip or knee osteoarthritis is inconsistent. Total joint replacement is considered a surrogate measure for symptomatic end-stage osteoarthritis. We examined the relationship between HFE gene mutations and risk of total hip and knee replacement using a prospective cohort study.


METHODS
The Melbourne Collaborative Cohort Study recruited participants between 1990 and 1994. Participants born in Australia, New Zealand, the United Kingdom, or Ireland (n = 27,848) were genotyped for the HFE C282Y mutation. Total hip and knee replacements for osteoarthritis during 2001 to 2009 were ascertained from the Australian Orthopaedic Association National Joint Replacement Registry. Hazard ratios (HR)/odds ratios (OR) and confidence intervals (CI) were obtained from Cox regression or logistic regression.


RESULTS
Compared with those with no C282Y mutation, C282Y homozygotes had an increased risk of single total hip replacement (HR 1.94, 95% CI 1.04-3.62) and bilateral total hip replacement (OR 5.86, 95% CI 2.36-14.57) for osteoarthritis, adjusting for age, sex, body mass index, and educational level. Only 3 C282Y homozygotes had single total knee replacement; the HR was 0.51 (95% CI 0.16-1.57). C282Y/H63D compound heterozygosity was not related to the risk of total hip or knee replacement.


CONCLUSIONS
HFE C282Y homozygosity was associated with an increased risk of both single and bilateral total hip replacement for osteoarthritis.
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia.
Yuanyuan
Y
Wang
Lyle C
LC
Gurrin
Anita E
AE
Wluka
Nadine A
NA
Bertalli
Nicholas J
NJ
Osborne
Martin B
MB
Delatycki
Graham G
GG
Giles
Dallas R
DR
English
John L
JL
Hopper
Julie A
JA
Simpson
Stephen
S
Graves
Katrina J
KJ
Allen
Flavia M
FM
Cicuttini
D000328:Adult; D000368:Aged; D019644:Arthroplasty, Replacement, Hip; D001315:Australia; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007494:Ireland; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009520:New Zealand; D015207:Osteoarthritis, Hip / Q000235:genetics* / Q000601:surgery*; D011446:Prospective Studies; D012306:Risk; D006113:United Kingdom
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins