Angiotensin-converting enzyme and p22(phox) polymorphisms and the risk of coronary heart disease in a low-risk Spanish population.
OBJECTIVE
To evaluate the genetic contribution to myocardial infarction in a homogeneous Caucasian population (a Mediterranean Spanish population) with very low frequency of coronary heart disease (CHD).


METHODS
We analyzed a total of 210 subjects, younger than 55 years, considered to be a low-risk population (104 cases of myocardial infarction and 106 control), and genotyped them (using polymerase chain reaction and sequencing) for the angiotensin-converting enzyme (ACE) insertion/deletion (ACE I/D) and for the C242T polymorphism of NADPH oxidase p22(phox). Also, we sequenced 23 alleles of the ACE gene (9 D and 14 I) for the region that includes the end of the intron 16 and the exon 17.


RESULTS
The ACE genotype-prevalence values for II, ID and DD were 4.81%, 28.85% and 66.34%, respectively, among the myocardial infarction patients, and 2.83%, 71.70% and 25.47% among controls. The statistical analysis comparing patients and controls revealed significant differences (chi(2)=25.09, P=0.00000055) between the two subpopulations. Also, we found a strong association between the genotype DD and the risk of suffering CHD (odds ratio (OR): 3.64; 95% CI: 2.37-8.07). The prevalence of the CC, TC and TT genotypes of p22(phox) gene among healthy controls proved to be 53.77%, 44.34% and 1.89%, while those of myocardial infarction were 58.65%, 39.42% and 1.93%, respectively. The association of C242T polymorphism of the p22(phox) gene with CHD was not statistically significant, (chi(2)=0.49, P=0.48). Logistic-regression analysis demonstrated that the independent risk factor for developing myocardial infarction was the DD genotype of ACE gene. Finally, our results indicate that alleles I and D of ACE gene are differentiated at three positions (nucleotide sites 14,480, 14,488 and 14,521) of which, the positions 14,480 and 14,488 were in absolute linkage disequilibrium.


CONCLUSIONS
Among subjects of a Mediterranean population with low risk for CHD, the presence of DD ACE genotype could be a risk factor for myocardial infarction, and we confirm the linkage disequilibrium between two nucleotide positions of the ACE gene and the polymorphism for an Alu insertion.
Mata-Balaguer
Trinidad
T
Departamento de Genética, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain.
de la Herrán
Roberto
R
Ruiz-Rejón
Carmelo
C
Ruiz-Rejón
Manuel
M
Garrido-Ramos
Manuel A
MA
Ruiz-Rejón
Fernando
F
D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D009252:NADPH Dehydrogenase / Q000235:genetics*; D019255:NADPH Oxidases; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase; D007703:Peptidyl-Dipeptidase A