title: Novel P143L polymorphism of the LCAT gene is associated with dyslipidemia in Chinese patients who have coronary atherosclerotic heart disease.
abstract: Coronary atherosclerotic heart disease (CAD) is a multifactorial disorder resulting from numerous gene-gene and gene-environment interactions. Lecithin:cholesterol acyltransferase (LCAT), a key enzyme in reverse cholesterol transport and the metabolism of high-density lipoprotein (HDL), is thought to be a candidate gene related to dyslipidemia and CAD. Variations in the LCAT gene were investigated in 190 CAD patients and 209 age- and gender-matched controls by denaturing high-performance liquid chromatography, and confirmed by sequencing and RFLP assay. In CAD patients, a novel single-nucleotide polymorphism (P143L) in exon 4 of the LCAT gene was discovered in nine males and two females (frequency of 5.79%), which was found in none of 209 controls. The genotype and allele distribution of P143L is significantly (P<0.04 ) higher in the low HDL-C subgroup than in the normal HDL-C subgroup in both male patients and all CAD patients. P143L was also found to be significantly (P<0.01) associated with the low HDL-C phenotype in both male patients and all CAD patients, with odds-ratios of 7.003 (95% CI 2.243-21.859) and 5.754 (95% CI 1.893-13.785), respectively. Thus, the P143L polymorphism may play a role in causing decreased HDL-C levels, leading to increased risk of dyslipidemia and CAD in Chinese.
authors.affiliation: Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu 610041, China. kelanzhang@hotmail.com
authors.forename: Kelan
authors.initials: K
authors.lastname: Zhang
authors.forename: Sizhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Keqin
authors.initials: K
authors.lastname: Zheng
authors.forename: Yiping
authors.initials: Y
authors.lastname: Hou
authors.forename: Linchuan
authors.initials: L
authors.lastname: Liao
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Nebert
authors.forename: Jiajun
authors.initials: J
authors.lastname: Shi
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Su
authors.forename: Cuiying
authors.initials: C
authors.lastname: Xiao
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D007862:Phosphatidylcholine-Sterol O-Acyltransferase