Citation Information :
Kumar BV, Ramadevi K. Association of Dimethylarginine Dimethylaminohydrolase 2 (DDAH-2 1154 C > A) Gene Polymorphism with Coronary Artery Disease. Indian J Med Biochem 2020; 24 (3):99-103.
Background: Coronary artery disease is one of the most common causes of death. The initiation of atherosclerosis is due to endothelial dysfunction and is mainly due to decreased nitric oxide bioavailability. The nitric oxide is synthesized from L-arginine by endothelial nitric oxide synthase. The nitric oxide synthase inhibitor has been identified namely asymmetric dimethylarginine (ADMA). The major route of degradation of ADMA is by the dimethylarginine dimethylaminohydrolase enzymes. The gene silencing studies in rats have shown that the dimethylarginine dimethylaminohydrolase (DDAH) enzyme through the degradation of ADMA, regulates the function of nitric oxide synthase. Therefore, this study was undertaken to find the association of DDAH-2 gene polymorphisms with coronary artery disease.
Aims and objectives: The objective of the study is to find out the association of DDAH-2 gene (1151 C/A) polymorphism with coronary artery disease. To estimate the serum nitric oxide levels and find its relationship with the above gene polymorphism.
Materials and methods: Case-control study. One hundred cases of coronary artery disease in the age group between 35 years and 60 years old verified by coronary angiogram having >50% stenosis of at least one of the major coronary arteries were randomly recruited. Cases may be with or without risk factors like smoking, alcohol, and hypertension. Age, sex, and risk factors matched 100 controls who had no clinical evidence of coronary artery disease were selected. Assessment of DDAH-2 (1154 C > A) gene polymorphism was done by TaqMan assay using real-time PCR and confirmation of SNP genotypes was done by Sanger sequencing.
Results: AA genotype of DDAH-2 was significantly higher among cases (29%) when compared with controls (14%) with a statistically significant p value of 0.009. The odds ratio of 2.1 showed that subjects with the A+ allele carry a higher risk for coronary artery disease when compared with the A− allele. The serum nitric oxide was significantly lower in the AA genotype when compared with the CA and CC genotypes of the DDAH2 gene.
Conclusion: In this study, there is a good association of the A allele of DDAH-2 with the development of coronary artery disease (odds ratio of 2.19). Thus, A allele may be an independent risk factor for coronary artery disease. Multiple logistic regression predicts AA genotype as a significant and independent predictor of coronary artery disease.
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