Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-07-01
|
| Series: | Journal of Cardiovascular Development and Disease |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2308-3425/5/3/38 |
| _version_ | 1818131050193223680 |
|---|---|
| author | Rashid Mir Musadiq Bhat Jamsheed Javid Chandan Jha Alpana Saxena Shaheen Banu |
| author_facet | Rashid Mir Musadiq Bhat Jamsheed Javid Chandan Jha Alpana Saxena Shaheen Banu |
| author_sort | Rashid Mir |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T08:14:46Z |
| format | Article |
| id | doaj.art-6c866081bc7b4199956530af2403ef68 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-12-11T08:14:46Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-6c866081bc7b4199956530af2403ef682022-12-22T01:14:47ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252018-07-01533810.3390/jcdd5030038jcdd5030038Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery DiseaseRashid Mir0Musadiq Bhat1Jamsheed Javid2Chandan Jha3Alpana Saxena4Shaheen Banu5Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi ArabiaDepartment of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, IndiaDepartment of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi ArabiaDepartment of Human Genetics, Punjabi University, Patiala 147002, IndiaDepartment of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, IndiaDepartment of Biochemistry, Sri Jayadeva Institute of Cardio-vascular Science & Research & Karnataka Institute of Diabetology, Bangalore 560069, IndiaPurpose: 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.http://www.mdpi.com/2308-3425/5/3/38catechol-O-methyltransferase (COMT)coronary artery disease (CAD)allele specific PCR-AS-PCRCOMT Val158MetCOMT G >A |
| spellingShingle | Rashid Mir Musadiq Bhat Jamsheed Javid Chandan Jha Alpana Saxena Shaheen Banu Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease Journal of Cardiovascular Development and Disease catechol-O-methyltransferase (COMT) coronary artery disease (CAD) allele specific PCR-AS-PCR COMT Val158Met COMT G > A |
| title | Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease |
| title_full | Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease |
| title_fullStr | Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease |
| title_full_unstemmed | Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease |
| title_short | Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease |
| title_sort | potential impact of comt rs4680 g gt a gene polymorphism in coronary artery disease |
| topic | catechol-O-methyltransferase (COMT) coronary artery disease (CAD) allele specific PCR-AS-PCR COMT Val158Met COMT G > A |
| url | http://www.mdpi.com/2308-3425/5/3/38 |
| work_keys_str_mv | AT rashidmir potentialimpactofcomtrs4680ggtagenepolymorphismincoronaryarterydisease AT musadiqbhat potentialimpactofcomtrs4680ggtagenepolymorphismincoronaryarterydisease AT jamsheedjavid potentialimpactofcomtrs4680ggtagenepolymorphismincoronaryarterydisease AT chandanjha potentialimpactofcomtrs4680ggtagenepolymorphismincoronaryarterydisease AT alpanasaxena potentialimpactofcomtrs4680ggtagenepolymorphismincoronaryarterydisease AT shaheenbanu potentialimpactofcomtrs4680ggtagenepolymorphismincoronaryarterydisease |