Both alleles of the M235T polymorphism of the angiotensinogen gene can be a risk factor for myocardial infarction.
We have studied the role of three polymorphic genes of the renin-angiotensin system (RAS) as independent risk factors for myocardial infarction (MI) and their correlation with three of the major coronary risk factors: serum cholesterol (CH), hypertension (HT) and smoking (SM). A population of 392 men was genotyped for the M235T polymorphism of the angiotensinogen (AGT) gene, the insertion/deletion of the angiotensin-converting enzyme (ACE) and the all66c of the angiotensin-II type 1 receptor (AT1R), by means of polymerase chain reaction (PCR) and restriction enzyme analysis. It was observed that the T allele frequency increased significantly in the MI with HT, CH, and SM subgroup (0.58 vs 0.31) (p<0.01). In contrast, the M allele frequency was higher in the MI without HT, CH, and SM (0.69 vs 0.42) (p<0.01). A strong association between the MM genotype and MI (p<0.001, odds ratio=4.29, confidence interval=1.95-9.42) was found when age-matched MM control subjects were compared to MI individuals with none of the other known major coronary risk factors. Futhermore, subjects with the MM genotype showed a significantly higher plasma renin activity (PRA) profile than those with the TT genotype (p<0.001). It can be concluded that the M allele is an independent risk factor for MI and the T allele modified the risk when other major risk factors are present.
Fernández-Arcás
N
N
Department of Biochemistry and Molecular Biology, University of Málaga, Málaga, Spain.
Dieguez-Lucena
J L
JL
Muñoz-Morán
E
E
Ruiz-Galdón
M
M
Espinosa-Caliani
S
S
Aranda-Lara
P
P
Rius-Diaz
F
F
Gaitán-Arroyo
M J
MJ
De Teresa-Galván
E
E
Reyes-Engel
A
A
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D000808:Angiotensinogen / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D004247:DNA; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A; D012083:Renin