Association of Sp1 tandem repeat polymorphism of ALOX5 with coronary artery disease in Indian subjects.
Lipoxygenases have been implicated in the pathogenesis of coronary artery disease (CAD) for its potent proinflammatory role. The Sp1 addition/deletion polymorphism in promoter region of the 5-lipoxygenase gene (ALOX5) has been associated with increased risk of carotid atherosclerosis and myocardial infarction. To determine the role of this polymorphism in our population we performed a case-control-genetic association study on 117 healthy controls and 119 angiographically verified CAD patients. Biochemical analysis was performed using standard automated assays. High-density lipoprotein cholesterol (HDL-C) and LDL-C subfraction levels were estimated using precipitation methods. Genotyping of polymorphism in the ALOX5 (Sp1 variants) was done using PCR-based heteroduplex analysis and automated sequencing. The Sp1 promoter repeat variants were found to be associated with CAD (p < 0.0001, OR = 4.47, 95% confidence interval = 2.58-7.74). Furthermore, the 5/5 genotype of the ALOX5 polymorphism in the healthy subjects was found to be associated with elevated HDL-C (p= 0.004), HDL(3) -C (p= 0.04), apo A1 (p= 0.011) and sdLDL (p= 0.001). We conclude that this polymorphism influences LDL and HDL subfraction levels and is a risk factor for CAD in our population. Clin Trans Sci 2012; Volume 5: 408-411.
Research Laboratories, P. D. Hinduja National Hospital and Medical Research Centre, V. S. Marg, Mahim, Mumbai, India.
Seema P
SP
Todur
Tester F
TF
Ashavaid
D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008875:Middle Aged; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D020080:Tandem Repeat Sequences / Q000235:genetics*
D009692:Nucleic Acid Heteroduplexes; D016329:Sp1 Transcription Factor; D001094:Arachidonate 5-Lipoxygenase; C583212:ALOX5 protein, human