Identification of gene polymorphism in lipocalin-type prostaglandin D synthase and its association with carotid atherosclerosis in Japanese hypertensive patients.
Recent reports suggested that lipocalin-type prostaglandin D synthase (L-PGDS) is implicated in atherogenesis. In the present study, we investigated the polymorphism of the L-PGDS gene and examined its relationship with the severity of carotid atherosclerosis which is determined as the maximum intima-media thickness in the common carotid artery (C-IMT(max)). We identified 6 single nucleotide polymorphisms (SNPs) of the L-PGDS gene in Japanese. A rare SNP with an amino acid change (1535C>G in exon 4, Leu79Val) and a common SNP (4111 A>C in 3'-untranslated region) were selected for genotyping in 782 Japanese hypertensive subjects. There was no significant difference among genotypes in 1535C>G, however, in 4111 A>C, serum levels of high-density lipoprotein (HDL) cholesterol were significantly higher in subjects with A/A genotype than those with A/C and C/C genotypes. C-IMT(max) was significantly smaller in subjects with A/A genotype than those with A/C and C/C. Logistic regression analysis revealed that the presence of A/A genotype significantly reduced the risk for increased C-IMT(max), even after adjustment for other known risk factors [adjusted odds ratio: 0.71 (95% CI: 0.58-0.88)]. Our results suggested that 4111 A>C polymorphism in the L-PGDS gene contributes to the development of carotid atherosclerosis in Japanese hypertensive patients.
Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Japan. ymiwa@clipharm.med.kyushu-u.ac.jp
Yoshikazu
Y
Miwa
Shin
S
Takiuchi
Kei
K
Kamide
Masayoshi
M
Yoshii
Takeshi
T
Horio
Chihiro
C
Tanaka
Mariko
M
Banno
Toshiyuki
T
Miyata
Toshiyuki
T
Sasaguri
Yuhei
Y
Kawano
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000235:genetics*; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000473:pathology; D002340:Carotid Artery Diseases / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications*; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D007564:Japan; D054834:Lipocalins; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D017422:Sequence Analysis, DNA
D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase