| Coronary heart disease (CHD) is one of the leading causes of death worldwide. A strong inverse relationship between plasma HDL-C level and CHD risk has been confirmed in a large number of epidemiological studies. The protective effect of HDL against atherosclerosis and CHD might be related to its key role in the transport of cholesterol from peripheral cells to the liver, an antiatherogenic process known as reverse cholesterol transport (RCT) .ATP-binding cassette transporter A1 (ABCA1) gene encodes the membrane protein that participates in the biogenesis of HDL by stimulating cholesterol and phospholipid efflux to lipid poor apoA-I particles. Therefore, ABCA1 plays a crucial role in the initial steps of both the production of HDL and RCT. It has been demonstrated that mutations in the ABCA1 gene are responsible for some rare phenotypic consequences characterised by decreased plasma HDL-C level and increased risk of premature coronary atherosclerosis. Moreover, some common single nucleotide polymorphisms (SNP) in the ABC A1 gene have been shown to affect plasma levels as well as CHD risk by altering the activity or dose of product of ABC A1 gene expression.In the present study, possible association of 3 known SNPs in the ABCA1 gene and CHD or plasma lipids were carried out and screening for the possible new SNPs in some of exons of the ABCA1 gene wereperformed in a Chinese population including 264 CHD patients and 278 healthy controls using polymerase chain reaction, restriction fragment length polymorphism, denaturing high performance liquid chromatography and DNA sequencing approaches. The results are as follows:1. The frequencies of K allele frequency and KK genotype of R219K in controls were significantly higher than those in patients. When the patients were divided into two subgroups by onset-age, the frequencies of K allele and KK genotype for early-onset patients were lower than those for late-onset patients and those for controls; No significant differences of plasma high density lipoprotein cholesterol (HDL-C) levels were observed among patients with different genotypes while patients with RR genotype had a higher plasma concentration of triglycerides than that of KK genotype.These data suggest that the R219K polymorphism may be correlated with CHD, and the ABCAl gene KK genotype may has a function against atherosclerosis without detectable change of plasma HDL-C levels in Chinese .2. The distributions of I883M, C69T allelic frequencies did not significantly differ between patients and controls; In women patients, MM genotype in the I883M polymorphism was associated with higher HDL-C levels when compared with IM genotype.3. General linear model suggested that the genotypes of I883M polymorphism was associated with HDL-C levels, explaining 0.28% and 0.36% of the variation in the serum HDL-C levels only in women patients and women controls, respectively, which suggested that common variants in the ABCAl gene are not major determinant of plasma HDL-C levels ingeneral population.4. Through ABCA1 gene screening including parts of exons and adjacent intronic regions, 3847bp in total, 3 novel SNPs were identified, namely G4594A in exon 31, +132208G/A in intron 38 and +142785G/C in intron 49.5. Among the three novel SNPs , the frequencies of C allele and GC genotype of +142785G/C polymorphism for patients was significantly higher than that for controls.After stratification according to serum HDL-C levels, The frequencies of C allele and GC genotype were more frequent in the subgroup with low HDL-C level than that with normal HDL-C level,suggesting that +142785G/C polymorphism seemed to modify CHD risk by influencing plasma HDL-C levels.
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