Prevalence of hemochromatosis-related symptoms among individuals with mutations in the HFE gene.
OBJECTIVE
To determine the prevalence of hemochromatosis-related symptoms in homozygotes for the HFE mutation C282Y compared with controls without HFE mutations identified through a large screening program of subjects attending a health appraisal center.


METHODS
Presence of symptoms commonly associated with clinical hemochromatosis was ascertained by self-report on a written questionnaire among C282Y homozygotes and HFE wild-type subjects of white or Hispanic ethnicity identified from screening 41,599 adult subjects between March 1999 and August 2001. A subset of C282Y homozygotes and wild-type subjects identified from 12,756 subjects attending the center in the final year of the study completed a standardized double-blind interview with a physician regarding the presence, duration, and severity of a larger set of symptoms. Prevalence of symptoms among C282Y homozygotes and wild-type controls ascertained by written questionnaire and interview were compared by chi2 analysis or Fisher exact test. Symptoms among subjects with other combinations of the C282Y and H63D HFE mutations were also assessed by questionnaire.


RESULTS
The 124 C282Y homozygotes who filled out the written questionnaire and the 17 C282Y homozygotes who completed the physician double-blind interview reported no significantly higher rates of arthritis or joint pain, abdominal pain, arrhythmias, darkening of skin, or other symptoms traditionally associated with hemochromatosis compared with the 22,429 wild-type controls who filled out the written questionnaire and 29 wild-type controls who completed the double-blind interview. The only symptom reported more frequently by C282Y homozygotes was loss of body hair, reported by 5 C282Y/C282Y female subjects compared with 1 wild-type male subject (P=.02) in the physician interview. Symptoms among subjects with other HFE genotypes were similar to symptoms of wild-type subjects.


CONCLUSIONS
Results of this study indicate that many of the symptoms associated with hemochromatosis are common among HFE wild types and that clinical penetrance of the C282Y/C282Y genotype in regard to these symptoms is low.
Waalen
Jill
J
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. jwaalen@scripps.edu
Felitti
Vincent
V
Gelbart
Terri
T
Ho
Ngoc J
NJ
Beutler
Ernest
E
D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000235:genetics; D016022:Case-Control Studies; D003545:Cysteine / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011795:Surveys and Questionnaires; D014168:Transferrin / Q000378:metabolism; D014443:Tyrosine / Q000235:genetics; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
D014168:Transferrin; D001224:Aspartic Acid; D014443:Tyrosine; D006639:Histidine; D005293:Ferritins; D003545:Cysteine