title: Potentially protective effects of the Ser447-Ter mutation of the lipoprotein lipase gene against the development of coronary artery disease in Japanese subjects via a beneficial lipid profile.
abstract: Several DNA variants at the lipoprotein lipase (LPL) gene locus have been found to be associated with the plasma lipid levels and the prevalence of coronary artery disease (CAD). In particular, the Ser447-termination (Ter) mutation at the exon 9 of the LPL gene has the potential to elevate the plasma high-density lipoprotein (HDL) levels, but it remains unknown in the Japanese population. The present study investigated 93 CAD patients and 96 age- and sex-matched healthy controls. The Ser447-Ter mutation was determined by polymerase chain reaction restriction fragment length polymorphism method. The allelic frequency of the Ser447-Ter mutation was 0.103 in all subjects. The Ser447-Ter (GG and CG) group was associated with significantly higher levels of plasma HDL-cholesterol (p<0.001) and lower levels of plasma triglyceride than the CC group (p<0.02). The peak particle size of low-density lipoprotein (LDL) was significantly larger in the Ser447-Ter (GG and CG) group than in CC group (p<0.05). The frequency of the Ser447-Ter genotype in GG and CG was significantly lower in CAD than in the controls (11.9% vs 26%, odds ratio = 0.38; 95% confidence interval, 0.18-0.81; p<0.02). These results suggest that the Ser447-Ter mutation of the LPL gene is associated with high plasma HDL-cholesterol levels, low plasma triglyceride levels and a larger LDL particle size. This mutation may have a protective effect against the development of CAD via its favorable lipoprotein profile.
authors.affiliation: Department of Cardiology, Juntendo University, Tokyo, Japan. shinzen@beige.ocn.ne.jp
authors.forename: M
authors.initials: M
authors.lastname: Sawano
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Ohmura
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Daida
authors.forename: H
authors.initials: H
authors.lastname: Mokuno
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
mesh_terms: D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010316:Particle Size; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase