Carriers of three polymorphisms of cholesteryl ester transfer protein gene are at increased risk to coronary heart disease in a Chinese population.
BACKGROUND
The cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport of cholesterol from the peripheral tissue to the liver and the polymorphism in the CETP gene may therefore alter the susceptibility to coronary heart disease (CHD). The aim of the present study was to screen the CETP gene for new single nucleotide polymorphisms (SNPs) and to determine whether SNPs at important cholesterol metabolism gene loci might exert effects on the risk to CHD in Chinese.


METHODS
Genomic DNA samples were collected from 203 Chinese patients with CHD and 209 age- and gender-matched controls. The coding region, adjacent intronic sequences and promoter region (totally 5501 bp) of the CETP gene were screened based on a combination of polymerase chain reaction, denaturing high performance liquid chromatography and DNA sequencing. The association of individual single nucleotide polymorphisms with CHD was assessed by univariate, multivariate analysis and haplotype analysis.


RESULTS
Fifteen SNPs were identified in the CETP gene including 12 novel ones, of which, 3 were in promoter region, 1 in exon 10, and other 9 in introns. The frequencies of -644C, +13054T, 296Q, and 442G alleles were considerably higher, while the frequency of +9907A allele lower, in CHD patients than those in controls (p=0.016, p=0.043, p=0.006, p=0.006, and p=0.029, respectively). The results of individual polymorphism analyses were confirmed by haplotype analysis for the combination of these 5 SNPs. The -644A/C, L296Q, and D442G polymorphisms were found to be associated with CHD in this Chinese population by multivariate analysis (p=0.009, p=0.024, and p=0.007, respectively). The adjusted odds ratio for the development of CHD for the -644C allele carriers was 1.63 compared with -644AA genotype (95% CI 1.05-2.78; p<0.01), 1.71 for the 296Q allele carriers relative to 296LL genotype (95% CI 1.10-2.89; p<0.05), and 1.31 for the 442G allele carriers relative to 442DD genotype (95% CI 1.02-2.56; p<0.01), respectively.


CONCLUSIONS
There is a significant relation between the polymorphisms in the CETP gene and the development of CHD, and individuals homozygous or heterozygous for the -644C, 296Q, and 442G alleles of the CETP gene are at increased risk to develop CHD in this Chinese population.
Zheng
Keqin
K
Department of Medical Genetics, West China Hospital and Division of Human Morbid Genomics, Key Laboratory of Biotherapy of Human Diseases of Ministry of Education, Sichuan University, Chengdu 610041, China.
Zhang
Sizhong
S
Zhang
Li
L
He
Yong
Y
Liao
Linchuan
L
Hou
Yiping
Y
Huang
Dejia
D
D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002681:China; D053480:Cholesterol Ester Transfer Proteins; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins