| ObjectivesATP binding cassette transporter (ABCA1) not only is a limited rate gene that control efflux of cellular cholesterol in health individuals and patients with CAD, but also correlates closely with AS and CAD . Single nucleotide polymorphisms (SNPs) are the most common patterns of ABCA1 gene mutations in health individuals and patients with CAD. A number of the present investigations have identified several SNPs in non-coding regions of ABCA1 which may be important for the appropriate regulation of ABCA1 expression(i.e. in the promoter, intronl and the 5'untranslated region). The phenotypic effects of these SNPs in the REGRESS population have been confirmed. Among others, for the G-191C variant a threefold increase in coronary events in patients with family history of CAD was evident, and the changes in AS and CAD occurred without detectable changes in plasma lipid levels. Our study aims at analysis of -191G/C SNP in the Han healthy and CAD population, and showing distribution frequency of -191G/C SNP and its effects on plasma lipids in healthy population and exploring the relations between -191G/C SNP and plasma lipid levels,and severity of coronary atherosclerotic lesions in patients with CAD. Simultaneously, it is widely accepted that AS is a special chronic inflammatory process being adjusted by inflammatory cytokine. But the mechanism is still unclear. We also analyze interleukin-1β (IL-1 β ) intercellular adhesion molecule-l(ICAM-l )and monocyte chemoattractant protein-1 (MCP-1) of the three -191G/C genotypes in CAD and healthy individuals in order to provide some new evidences on the mechanism of CAD.MethodsIndividuals in two groups were researched. The CAD group included 204 subjects with CAD (131 males, 73 females). The control group included 114 healthy individuals (75 males, 39 females). The differences in age and sexual distinction were not significant(p>0.05). Genomic DNA in white blood cell from venous blood was abstracted by reagent box. By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), -191G/C genotypes in promoter region of ABCA1 gene were analyzed in 204 CAD patients and 114 control individuals and distribution of the -191G/C genotypes was compared between CAD group and control group, different CAD clinical situations, and also different coronary atherosclerotic severity. The clinical indexes, which included total cholesterol (TC) triglyceride (TG) high-density lipoprotein cholesterol (HDL-C) low-density lipoprotein cholesterol (LDL-C) very low-density lipoprotein cholesterol (VLDL-C) and body mass index (BMI) associated with CAD, were also compared among the three genotypes in CAD and control group. In CAD group, we also measured IL-1β ICAM-1 and MCP-1 in plasma to compare among the three genotypes of-191G/C SNP.Results1. The -191G/C SNP exists in the healthy Han population of China. Distribution of the -191G/C genotypes were GG 59.7% (190), GC 30.2% (96) and CC 10.1%(32).2. Distribution frequency of the three genotypes was significantly different in control and CAD group (p<0.05). The proportion of the CC genotype was obviously higher in CAD group than in control group and the C allele was more frequent in CAD group than in control group (p<0.05, p<0.01).3. In CAD group, various distribution frequency of the -191G/C genotypes between acute coronary syndrome (ACS) group and stable angina pectoris (SAP) group was detected (p<0.05). The proportion of the CC genotype was obviously higher in ACS group than in SAP group and the C allele was more frequent in ACS group than in SAP group (p<0.05, p<0.01).4. There was an obviously different distribution frequency of the -191G/C genotypes in multi and single coronary artery lesion group (p<0.05). The proportion of the CC genotype in multi coronary artery lesions group was higher than in single coronary artery lesion group (p<0.05).5. There was an obviously different distribution frequency of the -191G/C genotypes in type A> B and C group of coronary artery lesion (p<0.05). There was an inapparent different distribution frequency of the -191G/C genotypes in type A and B^ B and C group (p>0.05). There was an obviously different distribution frequency of the -191G/C genotypes in type A and C group (p <0.05).6. No association between the three genotypes in plasma levels of TC ^ TGn HDL-C> LDL-C> VLDL-C and BMI was detected in Han CAD patients and control individuals.7. There was an obviously different between the GG and GC > CC genotype in IL-1 P and ICAM-1 in plasma (p<0.05, p<0.01) , but no different between the GC and CC genotype(p>0.05).8. No relativity was found between the -191G/C genotypes and MCP-1 inplasma.Conclusions1. The -191G/C SNP exists in the Han population of China.2. The -191G/C SNP might not only result in CAD but also associate with the severity of coronary atherosclerosis and the instability of CAD.3. The effects of the -191G/C SNP in AS and CAD occurred without detectable changes in plasma lipid level. The C allele may be patyogenic and G allete may be protective for CAD.4. The -191 G/C SNP might have influence on IL-1 P and ICAM-1 in plasma in CAD patients and control individuals.5. No relativity was found between the -191G/C genotypes and MCP-1 in plasma in CAD patients and control individuals.6. The potential mechanism of CAD by -191G/C SNP: The occurance and development of CAD may correlate with -191G/C SNP through up-regulating IL-1 P and ICAM-1, but not through affecting plasma lipids.
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