HMOX1 Gene Promoter Polymorphism is Not Associated with Coronary Artery Disease in Koreans
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: The heme oxygenase-1 gene ( HMOX1 ) promoter polymorphisms modulate its transcription in response to oxidative stress. This study screened for HMOX1 polymor- phisms and investigated the association between HMOX1 polymorphisms and coronary artery disease (CAD) in the Korean population. Methods: The study population consisted of patients with CAD with obstructive lesions (n=110), CAD with minimal or no lesions (n=40), and controls (n=107). Thirty-nine pa- tients with CAD with obstructive lesions underwent follow-up coronary angiography after six months for the presence of restenosis. The 5’-flanking region containing (GT)n repeats of the HMOX1 gene was analyzed by PCR. Results: The numbers of (GT)n repeats in the HMOX1 promoter showed a bimodal distri- bution. The alleles were divided into two subclasses, S25 and L25, depending on whether there were less than or equal to and more than 25 (GT)n repeats, respectively. The allele and genotype frequencies among groups were statistically not different. More subjects in the S25-carrier group had the low risk levels of high sensitivity C-reactive protein (hsCRP) for the CAD than those in the non-S25 carrier group ( P =0.034). Multivariate logistic re- gression analysis revealed that the genotypes of (GT)n repeats were not related to CAD status. The restenosis group in the coronary angiography follow-up did not show any sig- nificant difference in HMOX1 genotype frequency. Conclusions: The HMOX1 genotypes were not found to be associated with CAD, but the short allele carrier group contained more individuals with hsCRP values reflecting low risk of cardiovascular disease in the Korean population.
Abstract
Background: The heme oxygenase-1 gene ( HMOX1 ) promoter polymorphisms modulate its transcription in response to oxidative stress. This study screened for HMOX1 polymor- phisms and investigated the association between HMOX1 polymorphisms and coronary artery disease (CAD) in the Korean population. Methods: The study population consisted of patients with CAD with obstructive lesions (n=110), CAD with minimal or no lesions (n=40), and controls (n=107). Thirty-nine pa- tients with CAD with obstructive lesions underwent follow-up coronary angiography after six months for the presence of restenosis. The 5’-flanking region containing (GT)n repeats of the HMOX1 gene was analyzed by PCR. Results: The numbers of (GT)n repeats in the HMOX1 promoter showed a bimodal distri- bution. The alleles were divided into two subclasses, S25 and L25, depending on whether there were less than or equal to and more than 25 (GT)n repeats, respectively. The allele and genotype frequencies among groups were statistically not different. More subjects in the S25-carrier group had the low risk levels of high sensitivity C-reactive protein (hsCRP) for the CAD than those in the non-S25 carrier group ( P =0.034). Multivariate logistic re- gression analysis revealed that the genotypes of (GT)n repeats were not related to CAD status. The restenosis group in the coronary angiography follow-up did not show any sig- nificant difference in HMOX1 genotype frequency. Conclusions: The HMOX1 genotypes were not found to be associated with CAD, but the short allele carrier group contained more individuals with hsCRP values reflecting low risk of cardiovascular disease in the Korean population.
참고문헌 (32)
- Berliner JA, "Atherosclerosis: basic mechanism.Oxidation, inflammation, and genetics", Circulation, 91, pp.2488~2496 (1995)
- Lusis AJ, "Atherosclerosis", Nature, 407, pp.233~241 (2000)
- Jornot L, "Variable glutathione levels and expression of antioxidant enzymes in human endothelial cells", Am J Physiol, 264, pp.482~489 (1993)
- Maines MD, "Hemeoxygenase: function, multiplicity, regulatory mechanisms, and clinical applications", FASEB J, 2, pp.2557~2568 (1988)
- Ishikawa K, "Heme oxygenase-1 inhibits atherosclerotic lesion formation in LDL-receptor knockout mice", Circ Res, 88, pp.506~512 (2001)
- Ryter SW, "Protective functions of heme oxygenase-1 and carbon monoxide in the respiratory system", ANTIOXIDANTS REDOX SIGNALING, 9(12), pp.2157~2173 (2007), MARY ANN LIEBERT INC
- Exner M, "Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with restenosis after percutaneous transluminal angioplasty", J Endovasc Ther, 8, pp.433~440 (2001)
- Ono K, "A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese", Atherosclerosis, 173, pp.315~319 (2004)
- Kaneda H, "Heme oxygenase-1 gene promoter polymorphism is associated with coronary artery disease in Japanese patients with coronary risk factors", Arterioscler Thromb Vasc Biol, 22, pp.1680~1685 (2002)
- Schillinger M, "Heme oxygenase-1 genotype is a vascular anti-inflammatory factor following balloon angioplasty", J Endovasc Ther, 9, pp.385~394 (2002)
- Schillinger M, "Heme oxygenase-1 genotype and restenosis after balloon angioplasty: a novel vascular protective factor", J Am Coll Cardiol, 43, pp.950~957 (2004)
- Chen YH, "Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting", Eur Heart J, 25, pp.39~47 (2004)
- Pearson TA, "Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association", Circulation, 107, pp.499~511 (2003)
- Hansson GK, "Inflammation, atherosclerosis, and coronary artery disease", N Engl J Med, 352, pp.1685~1695 (2005)
- Chen M, "Short (GT) (n) repeats in heme oxygenase-1 gene promoter are associated with lower risk of coronary heart disease in subjects with high levels of oxidative stress", Cell Stress Chaperones, 17, pp.329~338 (2012)
- Chen YH, "Role of heme oxygenase-1 in the regulation of blood pressure and cardiac function", Exp Biol Med, 228, pp.447~453 (2003)
- Bai CH, "Shorter GT repeat polymorphism in the heme oxygenase-1 gene promoter has protective effect on ischemic stroke in dyslipidemia patients", J Biomed Sci, 17, pp.12~ (2010)
- Abraham NG, "Hemeoxygenase and the cardiovascular-renal system", Free Radic Biol Med, 39, pp.1~25 (2005)
- Bozkaya OG, "Prolonged unconjugated hyperbilirubinaemia associated with the haem oxygenase-1 gene promoter polymorphism", Acta Paediatr, 99, pp.679~683 (2010)
- Lee TS, "Simvastatin induces heme oxygenase-1: a novel mechanism of vessel protection", Circulation, 110, pp.1296~1302 (2004)
- Chen YH, "Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients", Hum Genet, 111, pp.1~8 (2002)
- Gulesserian T, "Clinical restenosis after coronary stent implantation is associated with the heme oxygenase-1 gene promoter polymorphism and the heme oxygenase-1 +99 G", C variant, 2005, pp.51, 1661~1665
- Yamada N, "Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema", Am J Hum Genet, 66, pp.187~195 (2000)
- Was H, "Hemeoxygenase-1 in tumor biology and therapy", Curr Drug Targets, 11, pp.1551~1570 (2010)
- Raval CM, "Heme oxygenase-1 in lung disease", Curr Drug Targets, 11, pp.1532~1540 (2010)
- Kanai M, "Neonatal hyperbilirubinemia in Japanese neonates: analysis of the heme oxygenase-1 gene and fetal hemoglobin composition in cord blood", Pediatr Res, 54, pp.165~171 (2003)
- 진호준, "The Heme Oxygenase-1 Genotype is a Risk Factor to Renal Impairment of IgA Nephropathy at Diagnosis, Which is a Strong Predictor of Mortality", Journal of Korean Medical Science, 24, pp.30~37 (2009), 대한의학회
- Funk M, "The effect of a promoter polymorphism in the heme oxygenase-1 gene on the risk of ischaemic cerebrovascular events: the influence of other vascular risk factors", Thromb Res, 113, pp.217~223 (2004)
- Kimpara T, "Microsatellite polymorphism in the human heme oxygenase-1 gene promoter and its application in association studies with Alzheimer and Parkinson disease", Hum Genet, 100, pp.145~147 (1997)
- Endler G, "A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with increased bilirubin and HDL levels but not with coronary artery disease", Thromb Haemost, 91, pp.155~161 (2004)
- Li P, "Inflammatory response to coronary artery bypass surgery: does the heme-oxygenase-1 gene microsatellite polymorphism play a role?", Chin Med J, 118, pp.1285~1290 (2005)
- Tiroch K, "Heme oxygenase-1 gene promoter polymorphism and restenosis following coronary stenting", Eur Heart J, 28, pp.968~973 (2007)
