RESUMEN
The aim of the work was to study polymorphism of atherosclerosis-related genes in patients with different forms of coronary heart disease (CHD) and chronic cerebral ischemia (CCI) in comparison with long-living subjects. Analysis included the distribution of genotypes and alleles of functional polymorphisms of lipid metabolism genes, viz. HindIII--polymorphism of lipoproteinase (LPL) gene; HhaI--polymorphism of apoE gene; TaqIB--polymorphism of cholesterol ether transfer protein (CETP) gene; I/D--polymorphism of angiotensin converting enzyme (ACE) in CHD and CCI patients of different age groups including long livers and those presenting with different clinical variants of CHD and CCI (FC II-III stable angina of effort, acute myocardial infarction, post-infarction cardiosclerosis, acute coronary syndrome) and control subjects. The study revealed potential molecular-genetic markers for primary and secondary prophylaxis of CHD and CCI. It was shown that DD genotypes of ACE gene, H+/+ of LPL gene and E3E4 are associated with an enhanced probability of myocardial infarction (IM) in CHD patients and can be regarded as high risk markers. The DD genotype is associated with an increased risk of recurrent MI, life-threatening post-IM complications and severe cardiac insufficiency as well as peculiar personality and behavioural traits (animosity and type A behaviour)--psychological risk factors of CHD and predictors of delayed application for medical aid. E2 allele of the ApoE gene and H allele of the LPL gene occur much more frequently in CHD patients aged above 90 years (long livers) than in younger subjects; hence, their value as markers of stable ischemic disease. Protective effect in terms of favourable clinical course of CCI and life expectancy is especially pronounced in subjects with a combination of genotypes with E2E3 + H+H-, E2E2 + H+H-, E3E3 + H-H-genes of ApoE and LPL. B2B2 genotype of CETP gene increases the risk of stable CCI and B1B1 genotype of CETP gene enhances predisposition to cardiovascular pathology.
Asunto(s)
Apolipoproteínas E/genética , Aterosclerosis/genética , Enfermedad Coronaria/genética , Metabolismo de los Lípidos/genética , Lipoproteína Lipasa/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Aterosclerosis/sangre , Enfermedad Coronaria/sangre , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Peptidil-Dipeptidasa A/sangreRESUMEN
The authors compare distribution of genotype frequencies and alleles of I/D of ACE gene polymorphism in patients with various forms of ischemic heart disease (IHD): with acute myocardial infarction (MI), stable effort angina (functional class II-III); in patients with postinfarction cardiosclerosis (PICS). A relationship was found between I/D polymorphism and acute MI. Frequency of DD genotype in MI patients was 0.57, in controls--0.21, p < 0.0001, RR = 4.9. The DD genotype may serve a marker of hereditary predisposition to MI. Genotype DD frequency in the group with acute MI was higher than that with PICS. In acute MI frequency of allele D was 0.76, in PICS--0.51, p < 0.0005. It is suggested that low frequency of genotype DD in the PICS group results from higher lethality of patients with DD genotype in the nearest rehabilitation period. Patients with repeated MI have a significantly higher frequency of genotype DD and complications after MI. Thus, there is a relationship between insertion-deletion polymorphism of ACE gene and myocardial infarction. Deletion DD genotype raises the risk to develop MI and probability of life-threatening complications and repeated MI.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/genética , Glicoproteínas de Membrana/genética , Infarto del Miocardio/genética , Peptidil-Dipeptidasa A , Polimorfismo Genético/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , HumanosRESUMEN
Allele and genotype frequencies of the HindIII polymorphism of the lipoprotein lipase (LPL) gene were studied in patients with myocardial infarction (MI) and stable angina of effort (SAE), including long-lived people (over 90). The polymorphism proved to be associated with MI and with the life span, genotype H+/H+ being predisposing to MI and allele H- being protective. The allele and genotype frequencies of long-lived people differed significantly from the Hardy-Weinberg proportions and from those of SAE patients aged up to 90. An excess of heterozygotes in this group suggests a selective pressure which eliminates homozygotes. Possibly, heterozygotes H+/H- have an adaptive advantage, which provides for their longevity.