Length polymorphism in heme oxygenase-1 and risk of CKD among patients with coronary artery disease.
The length polymorphism of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with cardiovascular events and mortality in high-risk populations. Experimental data suggest that heme oxygenase-1 protects against kidney disease. However, the association between this polymorphism and long-term risk of CKD in high-risk patients is unknown. We analyzed the allelic frequencies of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter in 386 patients with coronary artery disease recruited from January 1999 to July 2001 and followed until August 31, 2012. The S allele represents short repeats (<27), and the L allele represents long repeats (≥27). The primary renal end points consisted of sustained serum creatinine doubling and/or ESRD requiring long-term RRT. The secondary end points were major adverse cardiovascular events and mortality. At the end of study, the adjusted hazard ratios (95% confidence intervals) for each L allele in the additive model were 1.99 (1.27 to 3.14; P=0.003) for the renal end points, 1.70 (1.27 to 2.27; P<0.001) for major adverse cardiovascular events, and 1.36 (1.04 to 1.79; P=0.03) for mortality. With cardiac events as time-dependent covariates, the adjusted hazard ratio for each L allele in the additive model was 1.91 (1.20 to 3.06; P=0.01) for the renal end points. In conclusion, a greater number of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with higher risk for CKD, cardiovascular events, and mortality among patients with coronary artery disease.
Faculty of Medicine, Division of Nephrology, Department of Internal Medicine, Taipei City Hospital, Yang-Ming Branch, Taipei, Taiwan;
Yu-Hsin
YH
Chen
Division of Nephrology, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan;
Ko-Lin
KL
Kuo
Division of Nephrology, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan;
Szu-Chun
SC
Hung
Division of Geriatrics and Gerontology, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan; and.
Chih-Cheng
CC
Hsu
Faculty of Medicine, Divisions of Cardiology and yhchen@vghtpe.gov.tw dctarng@vghtpe.gov.tw.
Ying-Hwa
YH
Chen
Faculty of Medicine, Institute of Clinical Medicine, and Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan; Nephrology, Department of Medicine and Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan yhchen@vghtpe.gov.tw dctarng@vghtpe.gov.tw.
Der-Cherng
DC
Tarng
D000368:Aged; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000401:mortality*; D012307:Risk Factors
C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
CKD; coronary artery disease; guanosine thymidine dinucleotide; heme oxygenase-1; mortality; polymorphism