Identification of gene polymorphism in lipocalin-type prostaglandin D synthase and its association with carotid atherosclerosis in Japanese hypertensive patients.
Identification of gene polymorphism in lipocalin-type prostaglandin D synthase and its association with carotid atherosclerosis in Japanese hypertensive patients.
复制标题
DOI：
10.1016/j.bbrc.2004.07.143
复制
发表时间：
2004-09
影响因子：
3.1
通讯作者：
Y. Miwa;S. Takiuchi;K. Kamide;M. Yoshii;T. Horio;C. Tanaka;Mariko Banno;T. Miyata;T. Sasaguri;Y. Kawano
中科院分区：
文献类型：
--
作者：
Y. Miwa;S. Takiuchi;K. Kamide;M. Yoshii;T. Horio;C. Tanaka;Mariko Banno;T. Miyata;T. Sasaguri;Y. Kawano
最近的研究表明，Lipocalin型前列腺素D合成酶(L-PGDS)参与了动脉粥样硬化的形成。在本研究中，我们调查了L-前列腺素DS基因的多态性，并探讨了其与颈动脉粥样硬化程度的关系。我们在日本人中发现了L-PGDS基因的6个单核苷酸多态性(SNPs)。选择一个罕见的氨基酸突变的SNP(外显子4的1535C和GT；G，Leu79Val)和一个常见的SNP(3‘-非翻译区的4111A和GT；C)对782例日本高血压患者进行基因分型。1535C和GT；G等位基因携带者之间无显著差异，而4111A和GT；C等位基因携带者血清高密度脂蛋白胆固醇水平显著高于A/C和C/C携带者。C-IMTmax在A/A基因携带者中显著小于A/C和C/C基因携带者。Logistic回归分析显示，即使在调整了其他已知危险因素后，A/A基因携带者也显著降低了C-IMTmax升高的风险[调整的优势比：0.71(95%CI：0.58-0.88)]。我们的结果提示L-PGDS基因4111A和GT；C多态与日本高血压患者颈动脉粥样硬化的发生有关。
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-IMTmax). 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-IMTmaxwas 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-IMTmax, 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.