The Effects of CYP2A6 Gene Polymorphism on Cardiovascular Diseases

The CYP2A6 gene encodes its enzymes and is highly polymorphic, leading to variations in allele forms, both in the active and inactive states. These changes result in a decrease, increase or deletion of enzyme activities. One of the specific substrates is nicotine, an active compound in cigarettes. Nicotine is a major risk factor for cardiovascular diseases, and the inactive alleles tends to decrease its metabolism and expands the threat to infections. Therefore, this study aims to evaluate the effects of CYP2A6gene polymorphism on cardiovascular diseases. Relevant literatures were obtained using PubMed and Google Scholar, while the eventual selection followed the inclusion and exclusion criteria. Based on this review, the CYP2A6 gene polymorphism, both in increased, decreased or deleted alleles, was known to significantly influence nicotine metabolism and its blood levels. Species categorized as slow or poor metabolizers, tend to decrease the nicotine metabolism, but result in greater nicotine blood levels. This outcome subsequently accelerated the activation of the sympathetic nervous system, lipolysis, and insulin resistance, to trigger atherosclerosis. In summary, CYP2A6 gene polymorphism is known to increase cardiovascular diseases, particularly among active or passive smokers.

Association of CYP2A6 gene deletion with cancers in Japanese elderly: an autopsy study

Background CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial. Methods We undertook an association study to determine whether deletion of CYP2A6 gene associates with total cancer and major cancer types employing data of consecutive autopsy cases registered in the Japanese single-nucleotide polymorphisms for geriatric research (JG-SNP) database. The presence of cancer were inspected at the time of autopsy and pathologically confirmed. Genotyping for CYP2A6 wild type (W) and deletion (D) was done by allele specific RT-PCR method. Results Among 1373 subjects, 826 subjects (60.2%) were cancer positive and 547 subjects (39.8%) were cancer negative. The genotype frequency in the whole study group for WW, WD and DD were 65.0%, 30.6% and 4.4%, respectively, which obeyed the Hardy-Weinberg equilibrium (p=0.20). Total cancer presence, as well as major cancers including gastric, lung, colorectal, and blood cancers did not show any positive association with CYP2A6 deletion. When male and female were separately analyzed, CYP2A6 deletion associated with decreased gastric cancer risk in female (OR=0.49, 95%CI: 0.25-0.95, p=0.021, after adjustment for age, smoking and drinking). When smoker and non-smoker were separately analyzed, CYP2A6 deletion associated with decreased total cancer in female nonsmokers (OR=0.67, 95%CI: 0.45-0.99, p=0.041 after adjustment). On the other hand, CYP2A6 deletion associated increase blood cancers in smokers (OR=2.05, 95%CI: 1.19-3.53, p=0.01 after adjustment). Conclusion The CYP2A6 deletion may not grossly affect total cancer. It may associate with individual cancers in sex and smoking dependent manner. Further studies with larger sample size are warranted to confirm our results.

Association of CYP2A6 gene deletion with cancers in Japanese elderly: an autopsy study

Background CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial. Methods We undertook an association study to determine whether deletion of CYP2A6 gene associates with total cancer and major cancer types employing data of consecutive autopsy cases registered in the Japanese single-nucleotide polymorphisms for geriatric research (JG-SNP) database. The presence of cancer were inspected at the time of autopsy and pathologically confirmed. Genotyping for CYP2A6 wild type (W) and deletion (D) was done by allele specific RT-PCR method. Results Among 1373 subjects, 826 subjects (60.2%) were cancer positive and 547 subjects (39.8%) were cancer negative. The genotype frequency in the whole study group for WW, WD and DD were 65.0%, 30.6% and 4.4%, respectively, which obeyed the Hardy-Weinberg equilibrium (p=0.20). Total cancer presence, as well as major cancers including gastric, lung, colorectal, and blood cancers did not show any positive association with CYP2A6 deletion. When male and female were separately analyzed, CYP2A6 deletion associated with decreased gastric cancer risk in female (OR=0.49, 95%CI: 0.25-0.95, p=0.021, after adjustment for age, smoking and drinking). When smoker and non-smoker were separately analyzed, CYP2A6 deletion associated with decreased total cancer in female nonsmokers (OR=0.67, 95%CI: 0.45-0.99, p=0.041 after adjustment). On the other hand, CYP2A6 deletion associated increase blood cancers in smokers (OR=2.05, 95%CI: 1.19-3.53, p=0.01 after adjustment). Conclusion The CYP2A6 deletion may not grossly affect total cancer. It may associate with individual cancers in sex and smoking dependent manner. Further studies with larger sample size are warranted to confirm our results.

Association of CYP2A6 gene deletion with cancers in Japanese elderly: an autopsy study

Background CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial. Methods We undertook an association study to determine whether deletion of CYP2A6 gene associates with total cancer and major cancer types employing data of consecutive autopsy cases registered in the Japanese single-nucleotide polymorphisms for geriatric research (JG-SNP) database. The presence of cancer were inspected at the time of autopsy and pathologically confirmed. Genotyping for CYP2A6 wild type (W) and deletion (D) was done by allele specific RT-PCR method. Results Among 1373 subjects, the genotype frequency for WW, WD and DD were 65.0%, 30.6% and 4.4%, respectively, which obeyed the Hardy-Weinberg equilibrium. Association for total cancer presence, as well as major cancers including gastric, lung, colorectal, and blood cancers did not show any positive association. When male and female were separately analyzed, CYP2A6 deletion associated with decreased gastric cancer risk in female (OR=0.49, 95%CI: 0.25-0.95, p=0.021, after adjustment for age, smoking and drinking). When smoker and non-smoker were separately analyzed, CYP2A6 deletion associated with decreased total cancer in female nonsmokers (OR=0.67, 95%CI: 0.45-0.99, p=0.041 after adjustment). On the other hand, CYP2A6 deletion associated increase blood cancers in smokers (OR=2.05, 95%CI: 1.19-3.53, p=0.01 after adjustment). Conclusion The CYP2A6 deletion may not grossly affect total cancer. It may associate with individual cancers in sex and smoking dependent manner. Further studies with larger sample size are warranted to confirm our results.

COMPARISON OF CYTHOCROME P450 FAMILY 2 SUBFAMILY A POLYPEPTYDE 6 (CYP2A6) GENE POLYMORPHISM PROPORTION ON EARLY AND ADVANCED STAGE OF UNDIFFERENTIATED TYPE NASOPHARYNGEAL CARCINOMA IN BALINESE

Introduction Nasopharyngeal carcinoma (NPC) is a malignancy derived from epithelial cells lining the nasopharynx. The etiology of nasopharyngeal carcinoma is multifactorial. One of the risk factors is CYP2A6 gene polymorphism which causes nitrosamines are not metabolized, leading to DNA change that could trigger cancer. Objectives The purpose of this study is to know the association of CYP2A6 gene polymorphism and clinical stage of undifferentiated type of NPC Material and Method This is a cross sectional analytic study. The sample in this study were 80 nasopharyngeal carcinoma patients whose treated in ENT-HN department of Sanglah General Hospital between 2017 - 2018. The collected data consist of subject’s characteristic and CYP2A6 gene polymorphisms identified by the PCR-RFLP technique. Results The probability of CYP2A6 gene polymorphism in the undifferentiated type of NPC in the Balinese tribe is 3.125 times greater in advanced stage than early stage. Based on multivariate analysis, there was a statistically significant association between CYP2A6 gene polymorphism and clinical stage of undifferentiated type NPC in Balinese with p value = 0,0048 (p < 0,05). Conclusion There is association between CYP2A6 gene polymorphism and clinical stage of undifferentiated type NPC in Balinese tribe.

Associations of CYP2A6 Gene Polymorphism with Smoking Status Among Jordanians: Gender-Related Differences

Background: Cytochrome P450 2A6 enzyme (CYP2A6), an essential hepatic enzyme involved in the metabolism of drugs, is responsible for a major metabolic pathway of nicotine. Variation in the activity of polymorphic CYP2A6 alleles has been implicated in inter-individual differences in nicotine metabolism. Aims: The objective of the current study was to assess the association between the smoking status and the cytochrome P450 2A6 enzyme (CYP2A6) genotype in Jordanians. Methods: In the current study, 218 (117 Male and 101 female) healthy unrelated Jordanian volunteers were recruited. CYP2A6*1B, CYP2A6*4 and CYP2A6*9 were determined and correlated with subject smoking status. Results: *1A/*1A was the most common genetic polymorphism in the overall study population, with no significant frequency differences between smokers and non-smokers. When the population was divided according to gender, only male smokers showed a significant correlation between genotype and smoking status. Considering the CYP2A6*9 genotype, the results showed differences in distribution between smokers and non-smokers, but only women showed a significant association between CYP2A6*9 allele genotype and smoking status. Conclusion: The results of this study show that there is a significant association between CYP2A6*9 genotype and smoking status. They also show that CYP2A6 genotype is significantly influenced by gender.

Association of CYP2A6 gene deletion with cancers in Japanese elderly: an autopsy study

Background CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial.Methods We undertook an association study to determine whether deletion of CYP2A6 gene associates with total cancer and major cancer types employing data of consecutive autopsy cases registered in the Japanese single-nucleotide polymorphisms for geriatric research (JG-SNP) database. The presence of cancer were inspected at the time of autopsy and pathologically confirmed. Genotyping for CYP2A6 wild type (W) and deletion (D) was done by allele specific RT-PCR method.Results Among 1373 subjects, the genotype frequency for WW, WD and DD were 65.0%, 30.6% and 4.4%, respectively, which obeyed the Hardy-Weinberg equilibrium. Association for total cancer presence, as well as major cancers including gastric, lung, colorectal, and blood cancers did not show any positive association. When male and female were separately analyzed, CYP2A6 deletion associated with decreased gastric cancer risk in female (OR=0.49, 95%CI: 0.25-0.95, p=0.021, after adjustment for age, smoking and drinking). When smoker and non-smoker were separately analyzed, CYP2A6 deletion associated with decreased total cancer in female nonsmokers (OR=0.67, 95%CI: 0.45-0.99, p=0.041 after adjustment). On the other hand, CYP2A6 deletion associated increase blood cancers in smokers (OR=2.05, 95%CI: 1.19-3.53, p=0.01 after adjustment).Conclusion The CYP2A6 deletion may not grossly affect total cancer. It may associate with individual cancers in sex and smoking dependent manner. Further studies with larger sample size are warranted to confirm our results.