Polymorphisms In Intercellular Adhesion Molecule-1 Gene And Their Association With Coronary Heart Disease

Backgroundscardiovascular disease is the leading cause of illness and death in the developing countries. In 2000, approximately 946,000 deaths were attributable to cardiovascular disease, accounting for 39 percent of all deaths in the United States. Epidemiologic studies and randomized clinical trials have provided compelling evidence that coronary heart disease (CHD) is largely an inflammatory disease. However, there is also reason to believe that there is a heritable component to the disease. Up-regulation of intercellular adhesion molecule-1(ICAM-1) has been demonstrated in biopsies, and these molecules are known to regulate leukocyte migration. Several gene polymorphisms were reported in ICAM-1 molecule, and some of them were thouht to be related with diabetes mellitus, endometriosis, renal graft failure, and so on. So it was a hypothesis that it is associated with CHDObjectiveTo explore the distribution of Gly241Arg and Lys469Glu polymorphisms of ICAM-1 gene, and to assess the association between ICAM-1 gene polymorphisms and CHD in Hans of Chinese, as well as the interactions of the polymorphisms and the related risk factors of CHD.MethodsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR sequence-specific primers (PCR-SSP) were used for the detection of ICAM-1 genotypes in 211 patients with CHD and 206 healthy controls. Binary Logistic regression analysis was made to explore the risk factors for CHD. The serum slCAM-1 and high senstivity C-reactive protein (hsCRP) levels were measured by ELISA and turbidimetric method, respectively.ResultsThe frequencies of Lys/Lys, Lys/Glu and Glu/Glu Genotypes of Lys469Glu were 55.5% and 44.7%, 38.9% and 46.1%, 5.7% and 9.2%, patients andcontrols respectively. The frequence of Lys/Lys genotype in CHD patients was significantly higher than in controls (P<0.05), and the relative risk suffered from CHD of Lys/Lys genotype was 1.54 times of the Glu/Glu and Lys/Glu genotypes (Ofi=1.54, 95%C/: 1.05~2.27). In a multivariate Logistic regression analysis, hypertension, diabetes mellitus, cigarette smoking, high triglyceride (TG) levels, old age, white blood cell counting and genotype Lys/Lys were all associated with CHD. As for the interaction between gene and related exposure factors, genotype Lys/Lys strengthen the effect of hypertension and diabetes mellitus exposure (interaction index r>1.00, respectively), and weaken the effect of cigarette smoking exposure (r<1.00), both being multiplicative interaction model. However, we didn't detect the Gly241Arg polymorphism in our study. The serum slCAM-1 and hsCRP levels of the patients were significantly higher than that of the controls (P<0.05), however, among different genotypes, patients and controls respectively, there were no significantly differences.ConclusionsThe coding single nucleotide polymorphism (cSNP) at codon469 in the exon 6 of ICAM-1 gene is positively associated with the risk of CHD and the allele Lys may be a risk factor for CHD in Chinese, and an interaction exist between this genotype and related exposure factors. There is no Gly241Arg polymorphism in Chinese.