title: A novel polymorphism A(+884)-->G in the hepatic lipase gene and its association with coronary artery disease.
abstract: Hepatic lipase (HL) activity may influence susceptibility to coronary artery disease (CAD). Association between the single nucleotide polymorphisms (SNPs) in the HL gene with the occurrence of CAD has been investigated thoroughly, but to date most studies focused on the base variation in the promoter of HL gene, little is known about the variation in the coding region. In present study, the SNP in all exons of the HL gene were analyzed. All 9 exons with their flanking sequences of the HL gene were amplified from the Chinese patients with CAD and normal controls by PCR technique, and the PCR products were detected by denaturing high performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. As the result, a novel SNP A(+884)-->G within the sixth exon of HL gene was found, the 276 codon AAA was changed into AGA and resulted in the substitution of arginine for lysine. Compared with the control group, more CAD patients carried the G+884 allele (AG+GG) (54.9% vs. 41.5%, chi(2)=6.164, df=2, P=0.046). The prevalence of the G+884 allele was significantly higher in the CAD patients than that in control subjects (31.4% vs. 21.3%, chi(2) =4.652, df=1, P=0.031). Data from the linkage disequilibrium analysis showed that the A(+884)-->G polymorphism was strong in linkage disequilibrium with the T(-2)-->C variation we identified previously(D'=0.699, 0.742 in CAD patients and controls, respectively), and the frequency of the C(-2)/G(+884) haplotype (mutation) is significantly higher in CAD patients than that in controls (0.253 vs. 0.172, P<0.05).
authors.affiliation: Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Zhi-Guang
authors.initials: ZG
authors.lastname: Su
authors.forename: Si-Zhong
authors.initials: SZ
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Tong
authors.forename: Cui-Ying
authors.initials: CY
authors.lastname: Xiao
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hou
authors.forename: Lin-Chuan
authors.initials: LC
authors.lastname: Liao
mesh_terms: D003327:Coronary Disease / Q000235:genetics*; D005091:Exons; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D008049:Lipase