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J. Cardiovasc. Dev. Dis. 2018, 5(3), 38; https://doi.org/10.3390/jcdd5030038

Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease

1
Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
2
Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, India
3
Department of Human Genetics, Punjabi University, Patiala 147002, India
4
Department of Biochemistry, Sri Jayadeva Institute of Cardio-vascular Science & Research & Karnataka Institute of Diabetology, Bangalore 560069, India
*
Author to whom correspondence should be addressed.
Received: 23 May 2018 / Revised: 6 July 2018 / Accepted: 11 July 2018 / Published: 13 July 2018
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)
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Abstract

Purpose: Catechol-O-methyltransferase (COMT) plays a central role in DNA repair and estrogen-induced carcinogenesis. The nonsynonymous single nucleotide polymorphism (SNP) in exon 4 G > A or Val108 > 158Met or rs4680 G > A influences COMT enzyme activity. The three phenotypes of the COMT enzyme activities include COMT A/A with low enzyme activity, COMT A/G with medium enzyme activity and COMT G/G with high enzyme activity. The Met allele is associated with low enzymatic activity resulting in higher levels of prefrontal dopamine. Conversely, the Val allele is associated with high enzymatic activity and lower levels of prefrontal dopamine. The Met allele has been associated with several psychiatric disorders such as panic disorder. Many recent epidemiologic studies have investigated the association between the COMT Val158Met polymorphism and coronary artery diseases risk, but the results are inconclusive. Therefore our study was aimed to explore the association between COMT Val158Met polymorphism and the risk of coronary artery disease in India. Methology: This study was conducted on 100 clinically confirmed cases of coronary artery diseases and 100 healthy controls. COMT Val158Met genotyping was performed by allele-specific polymerase chain reaction (AS-PCR). Results: A significant correlation was observed in the COMT Val158Met genotype distribution between the coronary artery disease cases and healthy controls (p = 0.008). The frequencies of all three genotypes, GG, GA, AA, reported in the CAD patients were 10%, 70%, and 20%, and 30%, 60%, and 10% in the healthy controls respectively. An increased risk of coronary artery disease was observed in the codominant inheritance model for COMT-GA vs. GG genotype with an OR of 3.5, 95% CI (1.58–7.74) p = 0.002) and COMT-AA vs. GG genotype with an OR of 6.0 95% CI (2.11–17.3) p = 0.003). The higher risk of coronary artery disease was observed in the dominant inheritance model for COMT (GA + AA) vs. GG genotype (OR 3.85, 95% CI 1.76–8.4, p < 0.007), whereas a non-significant association was found in recessive model for COMT (GG + GA vs. AA) (OR = 2.01, 95% CI (0.86–4.7) p = 0.72). The results indicated that A allele significantly increased the risk of coronary artery disease compared to the G allele (OR = 1.8, 95% CI (1.20–2.67) p = 0.004). COMT Val158Met polymorphism leads to a 6.0, 3.5 and 1.8-fold increased risk of developing coronary artery disease in the Indian population and providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Conclusions: It is concluded that COMT-AA genotype and A allele are significantly associated with an increased susceptibility to coronary artery disease in Indian population. A larger sample size can be the key to progress in establishing the genetic co-relationship of COMT polymorphism and cardiovascular disease. View Full-Text
Keywords: catechol-O-methyltransferase (COMT); coronary artery disease (CAD); allele specific PCR-AS-PCR; COMT Val158Met; COMT G > A; catechol-O-methyltransferase (COMT); coronary artery disease (CAD); allele specific PCR-AS-PCR; COMT Val158Met; COMT G >; A;
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Mir, R.; Bhat, M.; Javid, J.; Jha, C.; Saxena, A.; Banu, S. Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease. J. Cardiovasc. Dev. Dis. 2018, 5, 38.

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