CETP (cholesteryl ester transfer protein) promoter -1337 C>T polymorphism protects against coronary atherosclerosis in Japanese patients with heterozygous familial hypercholesterolaemia.

Abstract

CETP (cholesteryl ester transfer protein) and HL (hepatic lipase) play a role in the metabolism of plasma lipoproteins, but the effects of CETP and LIPC (gene encoding HL) genotypes on coronary atherosclerosis may be dependent on LDL (low-density lipoprotein)-receptor activity. Recently, the -1337 C>T polymorphism in the CETP gene has been reported in REGRESS (Regression Growth Evaluation Statin Study) to be a major determinant of promoter activity and plasma CETP concentration. In the present study, we have investigated the effects of the CETP promoter -1337 C>T and LIPC promoter -514 C>T polymorphisms on serum lipid profiles and risk of coronary atherosclerosis in 206 patients (154 males) with heterozygous FH (familial hypercholesterolaemia). To evaluate coronary atherosclerosis, we used CSI (coronary stenosis index) calculated from coronary angiograms. The CETP -1337 T allele was less frequent in subjects with a CSI > or =14 (mean value) in the group with coronary artery disease (P=0.04, as determined by chi(2) test). ANOVA revealed that HDL-C (high-density lipoprotein-cholesterol) and triacylglycerol (triglyceride) levels were not significantly higher in the presence of the CETP promoter -1337 T allele. Combined with LIPC promoter polymorphisms, HDL-C levels were highest and CSI were lowest with CETP -1337 CT+TT and LIPC -514 CC genotypes, but a significant interaction was not shown. A multiple logistic regression analysis revealed that, in patients with coronary atherosclerosis, the CETP- 1337 CC genotype was a significant genetic risk factor in FH (odds ratio=2.022; P=0.0256). These results indicate that the CETP promoter -1337C>T polymorphism is associated with the progression of coronary atherosclerosis in Japanese patients with FH, independent of HDL-C and triacylglycerol levels.

• Authors: Mutsuko Takata, Akihiro Inazu, Shoji Katsuda, Kenji Miwa, Masa-Aki Kawashiri, Atsushi Nohara, Toshinori Higashikata, Junji Kobayashi, Hiroshi Mabuchi, Masakazu Yamagishi
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 111 Issue 5 Pg. 325-31 (Nov 2006) ISSN: 0143-5221 [Print] England
• PMID: 16822236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol Ester Transfer Proteins
• LIPC protein, human
• Lipids
• Lipase

Topics

• Adult
• Aged
• Aged, 80 and over
• Cholesterol Ester Transfer Proteins (blood, genetics)
• Coronary Artery Disease (blood, etiology, genetics)
• Disease Progression
• Female
• Genetic Predisposition to Disease
• Humans
• Hyperlipoproteinemia Type II (blood, complications, genetics)
• Lipase (genetics)
• Lipids (blood)
• Logistic Models
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic (genetics)
• Risk Factors
• Severity of Illness Index