Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States.
BACKGROUND
Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening.


OBJECTIVE
To estimate the prevalence of the HFE mutations C282Y and H63D in the US population.


METHODS
Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994.


METHODS
Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis.


METHODS
Estimates of the prevalence of C282Y and H63D mutations.


RESULTS
The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation.


CONCLUSIONS
Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.
Steinberg
K K
KK
Molecular Biology Branch, National Center for Environmental Health, Mailstop F-24, Chamblee, GA 30341, USA. kks1@cdc.gov
Cogswell
M E
ME
Chang
J C
JC
Caudill
S P
SP
McQuillan
G M
GM
Bowman
B A
BA
Grummer-Strawn
L M
LM
Sampson
E J
EJ
Khoury
M J
MJ
Gallagher
M L
ML
D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000453:epidemiology* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins; D020125:Mutation, Missense; D009749:Nutrition Surveys; D015995:Prevalence; D014481:United States / Q000453:epidemiology
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins