Association studies between haemochromatosis gene mutations and the risk of cardiovascular diseases.
BACKGROUND
Haemochromatosis is a common genetic disorder, inherited as an autosomal recessive trait that results in a progressive accumulation of iron in most tissues of the body. Positive association studies have been recently published between cardiovascular diseases and heterozygosity for the major mutation C282Y in the haemochromatosis gene HFE.


METHODS
In the present work, we have determined the HFE genotypes for C282Y and H63D in subjects from two case-control studies: the ECTIM and GENIC studies, designed to identify genetic variants associated with myocardial and brain infarction, respectively. In addition, we tested whether HFE mutations were associated with the degree of arteriosclerosis assessed non-invasively by Doppler ultrasonography on the carotid and femoral arteries, in a group of apparently healthy individuals (the AXA Study).


RESULTS
The prevalence of 282Y, and 63D allele carriers, did not differ between cases and controls in the ECTIM and in the GENIC studies, while 63D but not 282Y carriers were more numerous among subjects with atherosclerotic plaques in the AXA Study.


CONCLUSIONS
These three studies do not provide consistent evidence supporting the hypothesis that HFE mutations are associated with an increased risk of cardiovascular disease and with the development of arteriosclerosis.
Hetet
G
G
INSERM U409 and Association Claude Bernard, Paris, France, Salpêtrière Hospital, Paris, France.
Elbaz
A
A
Gariepy
J
J
Nicaud
V
V
Arveiler
D
D
Morrison
C
C
Kee
F
F
Evans
A
A
Simon
A
A
Amarenco
P
P
Cambien
F
F
Grandchamp
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D020520:Brain Infarction / Q000453:epidemiology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D003545:Cysteine / Q000235:genetics; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006639:Histidine / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D009660:Northern Ireland / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D011446:Prospective Studies; D014443:Tyrosine / Q000235:genetics; D014463:Ultrasonography; D006113:United Kingdom / Q000453:epidemiology
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D001224:Aspartic Acid; D014443:Tyrosine; D006639:Histidine; D003545:Cysteine