Apolipoprotein A1 gene polymorphisms and risk of early coronary disease.
Genetic studies have identified polymorphisms at the apolipoprotein (Apo) A1 gene associated with HDL cholesterol and apolipoprotein levels, and a relationship between the severity of coronary artery disease and polymorphisms at the 5'-end of Apo A1 has been also reported. This study was designed to examine the relationship between polymorphism at the Apo A1 gene and the risk of early coronary artery disease. Furthermore, the association of the polymorphism with the classical risk factors was analyzed. A total of 176 male patients (mean age 43 +/- 5 years) diagnosed as having unstable angina (53 cases) or myocardial infarction (123 cases) were prospectively evaluated. Data referring to hypertension, diabetes and tobacco consumption were recorded. The levels of total cholesterol, HDL cholesterol, Apo A1 and B and triglycerides were determined. DNA was obtained from the 176 patients and from 200 controls. In order to determine the Apo A1 genotypes at two polymorphic sites (G/A at -75 bp, and C/T at +83 bp), DNA was PCR amplified and digested with MspI. The frequency of carriers of the rare allele at the -75 bp site (M1-) was 0.34 in cases and 0.24 in controls (p < 0.05). The frequencies of the M1- allele among patients with angina and myocardial infarction were 0.43 (p = 0.009, angina vs. controls) and 0.30, respectively. No significant association between this polymorphism and other cardiovascular risk factors was found. No difference in the frequencies for carriers of the rare allele at the +83-bp polymorphism (M2) was observed among patients with angina (0.08 vs. 0.07) or myocardial infarction (0.04 vs. 0.07), and no association between this polymorphism and tobacco, hypertension and diabetes was noted. Patients carrying the rare M2- allele had a lower concentration of total cholesterol compared to those without this allele (183 +/- 29 vs. 223 +/- 54, p < 0.04) and HDL cholesterol was also lower among patients carrying the M2- (26 +/- 4 vs. 33 +/- 9, p < 0.02). In our community male patients with a diagnosis of coronary artery disease and age less than 50 years showed a higher frequency of the M1- allele at the -75-bp site of the Apo A1 gene. There was a significant increase in the frequency of the M1- allele in patients with unstable angina and no association with risk factors. In the +83-bp polymorphism there was no difference in the allelelic frequencies or the risk factors, except for the HDL cholesterol and total cholesterol where the patients with the allele M2- had lower levels than those homozygous for the M2+.
Reguero
J R
JR
Department of Cardiology, Instituto Reina Sofia de Investigación Nefrológica, Hospital Central de Asturias, Oviedo, Spain.
Cubero
G I
GI
Batalla
A
A
Alvarez
V
V
Hevia
S
S
Cortina
A
A
Coto
E
E
D000328:Adult; D000483:Alleles; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D001055:Apolipoproteins B / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics; D004247:DNA / Q000032:analysis*; D015342:DNA Probes / Q000737:chemistry; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D015342:DNA Probes; D005819:Genetic Markers; D014280:Triglycerides; D004247:DNA