Dataset Information

ApoB gene polymorphism (rs676210) and its pharmacogenetics impact on atorvastatin response among Iraqi population with coronary artery disease.

ABSTRACT:

Background

Drug response is below genetic influence, proven by the genetic variants. Pharmacogenetics trials are performed in many diseases, including coronary artery disease. This study was designed to determine the genetic polymorphism (rs676210) Pro2739leu G > A in the lipid metabolism-related gene (ApoB gene) and its pharmacogenetic role in the response to atorvastatin drug in a sample of Iraqi population with coronary artery disease (CAD).

Results

Significant differences of genotype distribution in CAD patients and controls were observed in ApoB_+ 8216 in Iraqi population from Hardy Weinberg Analysis. It also found that dramatic difference of low-density lipoprotein (LDL-C) level in response to 40 mg/day of atorvastatin therapy, the minor allele (A) observed a greater LDL-C lowering than the wild type allele (G). In ANOVA analysis, the result showed that the rs676210, Pro2739Leu, in ApoB gene increased non significantly, but gradually in plasma level of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), and oxidize low-density lipoprotein (oxLDL) in the order of genotype AA, GA, and GG in response to 40 mg atorvastatin.

Conclusion

We found the results highlighted the function of the rs676210, Pro2739Leu, in the ApoB gene in CAD etiology, and the findings support this variant's impact in predicting the response of (LDL-C) to 40 mg of atorvastatin therapy. ApoB gene polymorphism (rs676210, Pro2739Leu), specifically the AA genotype, may help to identify individuals who will profit from atorvastatin's lowering effects.

SUBMITTER: Abdulfattah SY

PROVIDER: S-EPMC8218108 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project 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.