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Polimorfisme Gen Sitokrom P450 2A6 Alel *1, *4, *7 dan *9 pada Subyek Uji Perokok Suku Thionghoa Indonesia Patramurti, Christine; Candaya, Evan Julian; Kiatarto, Stella Felina; Karut, Agnes Kurniati
Jurnal Farmasi Indonesia Vol 11, No 1 (2019)
Publisher : Indonesian Research Gateway

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.35617/jfi.v11i1.589

The CYP2A6 gene, encodes the CYP2A6 enzyme, has a highly polymorphism. These ezyme have played a role in nicotine metabolism, one of the active compounds in cigarettes that causes of cigarette dependence. The active form of the CYP2A6 gene allele is * 1 allele and some inactive forms of the CYP2A6 gene allele are * 4, * 7 and * 9 alleles. The inactive alleles would reduce the activity of the CYP2A6 enzyme. The genotypes of CY2A6 gene (CYP2A6* 1, * 4, * 7 and * 9) among Chinese Indonesian smokers were determined by allele-specific polymerase chain reaction (PCR) followed by electrophoresis method. The cigarette dependence was analyzed using the Fagerstrom Test for Nicotine Dependence (FTND) method.This study showed that there are CYP2A6 polymorphism genes among 30 smokers who participate in these study. The frequencies of the genotypes of CYP2A6 alleles were CYP2A6 *1/*1 (46.7%), CYP2A6 *1/*4 (16.7%), CYP2A6 *1/*7 (3.3%), CYP2A6 *1/*9 ( 10%), CYP2A6 *1/*4/*7 (6.7%), CYP2A6 *1/*4/*9 (10.0%), CYP2A6 *1/*7/*9 (3.3% ) and CYP2A6 *4/*7/* 9 (3.3%). The presence of inactive alleles can reduce the activity of the CYP2A6 enzyme in metabolizing nicotine, which can reduce the effects of cigarette dependence. The CYP2A6 gene, encodes the CYP2A6 enzyme, has a highly polymorphism. These ezyme have played a role in nicotine metabolism, one of the active compounds in cigarettes that causes of cigarette dependence. The active form of the CYP2A6 gene allele is * 1 allele and some inactive forms of the CYP2A6 gene allele are * 4, * 7 and * 9 alleles. The inactive alleles would reduce the activity of the CYP2A6 enzyme. The genotypes of CY2A6 gene (CYP2A6* 1, * 4, * 7 and * 9) among Chinese Indonesian smokers were determined by allele-specific polymerase chain reaction (PCR) followed by electrophoresis method. The cigarette dependence was analyzed using the Fagerstrom Test for Nicotine Dependence (FTND) method.This study showed that there are CYP2A6 polymorphism genes among 30 smokers who participate in these study. The frequencies of the genotypes of CYP2A6 alleles were CYP2A6 *1/*1 (46.7%), CYP2A6 *1/*4 (16.7%), CYP2A6 *1/*7 (3.3%), CYP2A6 *1/*9 ( 10%), CYP2A6 *1/*4/*7 (6.7%), CYP2A6 *1/*4/*9 (10.0%), CYP2A6 *1/*7/*9 (3.3% ) and CYP2A6 *4/*7/* 9 (3.3%). The presence of inactive alleles can reduce the activity of the CYP2A6 enzyme in metabolizing nicotine, which can reduce the effects of cigarette dependence. The CYP2A6 gene, encodes the CYP2A6 enzyme, has a highly polymorphism. These ezyme have played a role in nicotine metabolism, one of the active compounds in cigarettes that causes of cigarette dependence. The active form of the CYP2A6 gene allele is * 1 allele and some inactive forms of the CYP2A6 gene allele are * 4, * 7 and * 9 alleles. The inactive alleles would reduce the activity of the CYP2A6 enzyme. The genotypes of CY2A6 gene (CYP2A6* 1, * 4, * 7 and * 9) among Chinese Indonesian smokers were determined by allele-specific polymerase chain reaction (PCR) followed by electrophoresis method. The cigarette dependence was analyzed using the Fagerstrom Test for Nicotine Dependence (FTND) method.This study showed that there are CYP2A6 polymorphism genes among 30 smokers who participate in these study. The frequencies of the genotypes of CYP2A6 alleles were CYP2A6 *1/*1 (46.7%), CYP2A6 *1/*4 (16.7%), CYP2A6 *1/*7 (3.3%), CYP2A6 *1/*9 ( 10%), CYP2A6 *1/*4/*7 (6.7%), CYP2A6 *1/*4/*9 (10.0%), CYP2A6 *1/*7/*9 (3.3% ) and CYP2A6 *4/*7/* 9 (3.3%). The presence of inactive alleles can reduce the activity of the CYP2A6 enzyme in metabolizing nicotine, which can reduce the effects of cigarette dependence.

Polimorfisme Gen Sitokrom P450 2A6 Alel *1, *4, *7 dan *9 pada Subyek Uji Perokok Suku Thionghoa Indonesia Patramurti, Christine; Candaya, Evan Julian; Kiatarto, Stella Felina; Karut, Agnes Kurniati
Jurnal Farmasi Indonesia Vol 11, No 1 (2019)
Publisher : Jurnal Farmasi Indonesia

The CYP2A6 gene, encodes the CYP2A6 enzyme, has a highly polymorphism. These ezyme have played a role in nicotine metabolism, one of the active compounds in cigarettes that causes of cigarette dependence. The active form of the CYP2A6 gene allele is * 1 allele and some inactive forms of the CYP2A6 gene allele are * 4, * 7 and * 9 alleles. The inactive alleles would reduce the activity of the CYP2A6 enzyme. The genotypes of CY2A6 gene (CYP2A6* 1, * 4, * 7 and * 9) among Chinese Indonesian smokers were determined by allele-specific polymerase chain reaction (PCR) followed by electrophoresis method. The cigarette dependence was analyzed using the Fagerstrom Test for Nicotine Dependence (FTND) method.This study showed that there are CYP2A6 polymorphism genes among 30 smokers who participate in these study. The frequencies of the genotypes of CYP2A6 alleles were CYP2A6 *1/*1 (46.7%), CYP2A6 *1/*4 (16.7%), CYP2A6 *1/*7 (3.3%), CYP2A6 *1/*9 ( 10%), CYP2A6 *1/*4/*7 (6.7%), CYP2A6 *1/*4/*9 (10.0%), CYP2A6 *1/*7/*9 (3.3% ) and CYP2A6 *4/*7/* 9 (3.3%). The presence of inactive alleles can reduce the activity of the CYP2A6 enzyme in metabolizing nicotine, which can reduce the effects of cigarette dependence. The CYP2A6 gene, encodes the CYP2A6 enzyme, has a highly polymorphism. These ezyme have played a role in nicotine metabolism, one of the active compounds in cigarettes that causes of cigarette dependence. The active form of the CYP2A6 gene allele is * 1 allele and some inactive forms of the CYP2A6 gene allele are * 4, * 7 and * 9 alleles. The inactive alleles would reduce the activity of the CYP2A6 enzyme. The genotypes of CY2A6 gene (CYP2A6* 1, * 4, * 7 and * 9) among Chinese Indonesian smokers were determined by allele-specific polymerase chain reaction (PCR) followed by electrophoresis method. The cigarette dependence was analyzed using the Fagerstrom Test for Nicotine Dependence (FTND) method.This study showed that there are CYP2A6 polymorphism genes among 30 smokers who participate in these study. The frequencies of the genotypes of CYP2A6 alleles were CYP2A6 *1/*1 (46.7%), CYP2A6 *1/*4 (16.7%), CYP2A6 *1/*7 (3.3%), CYP2A6 *1/*9 ( 10%), CYP2A6 *1/*4/*7 (6.7%), CYP2A6 *1/*4/*9 (10.0%), CYP2A6 *1/*7/*9 (3.3% ) and CYP2A6 *4/*7/* 9 (3.3%). The presence of inactive alleles can reduce the activity of the CYP2A6 enzyme in metabolizing nicotine, which can reduce the effects of cigarette dependence. The CYP2A6 gene, encodes the CYP2A6 enzyme, has a highly polymorphism. These ezyme have played a role in nicotine metabolism, one of the active compounds in cigarettes that causes of cigarette dependence. The active form of the CYP2A6 gene allele is * 1 allele and some inactive forms of the CYP2A6 gene allele are * 4, * 7 and * 9 alleles. The inactive alleles would reduce the activity of the CYP2A6 enzyme. The genotypes of CY2A6 gene (CYP2A6* 1, * 4, * 7 and * 9) among Chinese Indonesian smokers were determined by allele-specific polymerase chain reaction (PCR) followed by electrophoresis method. The cigarette dependence was analyzed using the Fagerstrom Test for Nicotine Dependence (FTND) method.This study showed that there are CYP2A6 polymorphism genes among 30 smokers who participate in these study. The frequencies of the genotypes of CYP2A6 alleles were CYP2A6 *1/*1 (46.7%), CYP2A6 *1/*4 (16.7%), CYP2A6 *1/*7 (3.3%), CYP2A6 *1/*9 ( 10%), CYP2A6 *1/*4/*7 (6.7%), CYP2A6 *1/*4/*9 (10.0%), CYP2A6 *1/*7/*9 (3.3% ) and CYP2A6 *4/*7/* 9 (3.3%). The presence of inactive alleles can reduce the activity of the CYP2A6 enzyme in metabolizing nicotine, which can reduce the effects of cigarette dependence.

Implikasi Polimorfisme Gen CYP2A6 terhadap Penyakit Kardiovaskular Preiffer A. Prasojo; Christine Patramurti
Indonesian Journal of Clinical Pharmacy Vol 10, No 3 (2021)
Publisher : Universitas Padjadjaran

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15416/ijcp.2021.10.3.217

Gen CYP2A6 merupakan penyandi enzim CYP2A6. Gen CYP2A6 diketahui memiliki tingkat polimorfisme yang tinggi sehingga menyebabkan terdapatnya variasi bentuk alel baik dalam bentuk aktif maupun alel inaktif. Adanya variasi bentuk alel ini selanjutnya dapat berakibat pada penurunan, peningkatan atau penghilangan aktivitas enzim CYP2A6 yang disandi oleh gen ini. Salah satu substrat spesifik enzim CYP2A6 adalah nikotin, suatu senyawa aktif terdapat dalam rokok. Nikotin diketahui merupakan salah satu faktor risiko penyakit kardiovasakuler, sehingga kehadiran alel inaktif gen CYP2A6 akan menyebabkan penurunan aktivitas enzim CYP2A6 dalam metabolisme nikotin dan lebih lanjut akan meningkatkan risiko penyakit kardiovaskuler. Tujuan dari artikel review ini yaitu untuk mengevaluasi implikasi polimorfisme gen CYP2A6 terhadap penyakit kardiovaskular. Database yang digunakan pada artikel review ini berasal dari PubMed dan Google Scholar yang kemudian dilakukan seleksi dengan menggunakan kriteria inklusi dan eksklusi. Hasil yang diperoleh yaitu terdapat pengaruh polimorfisme gen CYP2A6 terhadap kandungan nikotin dalam darah terutama pada individu dengan gen CYP2A6 yang memiliki aktivitas metabolisme yang lambat atau buruk yang mengakibatkan kadar nikotin dalam darah yang tinggi, yang kemudian mengakibatkan peningkatan pengaktifan sistem saraf simpatis, lipolisis, dan resistensi insulin yang menyebabkan peningkatan kejadian anterosklerosis. Disimpulkan bahwa polimorfisme gen CYP2A6 akan meningkatkan penyakit kardiovaskuler terutama pada perokok, baik aktif maupun pasif.Kata kunci: Atherosklerosis, CYP2A6, penyakit kardiovasuler, polimorfisme The Effects of CYP2A6 Gene Polymorphism on Cardiovascular DiseasesAbstractThe 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. Keywords: Atherosclerosis, cardiovascular disease, CYP2A6, polymorphism

CYP2A6*4 allele gene high frequency associated with low-density lipoprotein cholesterol (LDL-C) among Javanese Indonesian smokers Preiffer Agus Prasojo; Christine Patramurti
Pharmaciana Vol 11, No 2 (2021): Pharmaciana
Publisher : Universitas Ahmad Dahlan

The CYP2A6 gene, which codes the CYP2A6 enzyme, has known to have ahigh polymorphism. This polymorphism could decrease, increase, or eliminate the CYP2A6 enzyme activity. CYP2A6*4, an inactive allele, decreased the CYP2A6 enzyme activity. One of the CYP2A6 enzyme-specific substrates is nicotine. This inactive allele could decrease nicotine metabolism that causes high nicotine levels in the blood. In addition, it caused the increasing levels of Low-Density Lipoprotein Cholesterol (LDL-C) by expanding the lipolysis process. The purpose of this research was to evaluate the effect of the CYP2A6*4 allele gene on LDL-C levels. Respondents in this study were 31 male Javanese smokers. This research is an analytic observational study with a cross-sectional design. Polymerase chain reaction (PCR) methods use to identification the CYP2A6*4 allele gene. This study shows that a high-frequency CYP2A6*4 alleles gene among the subject was detected, with an allele frequency is 93.55%. Furthermore, this CYP2A6*4 allele gene did not impact LDL-C levels, with the Odd Ratio value was 1.636 (P-Value = 0.737). In conclusion, the CYP2A6*4 allele gene does not significantly affect the LDL-C levels in Javanese Indonesian smokers.

Distribution of cytochrome P450*4 (CYP2A6*4) allele gene among Javanese Indonesian T2DM patients Christine Patramurti; Dita Maria Virginia
Pharmaciana Vol 11, No 1 (2021): Pharmaciana
Publisher : Universitas Ahmad Dahlan

Smoking had been increasing the risk factor of type 2 diabetes mellitus (T2DM), both active and passive smokers, which is caused by nicotine contained in cigarettes. Nicotine has metabolized by cytochrome p450 2a6 (CYP2A6) enzyme coded by the CYP2A6 gene. This gene was a high polymorphism that is the CYP2A6*4 allele gene was inactive. Thus, our objective was to describe the CYP2A6*4 allele gene among active and passive Javanese smokers with T2DM. From this cross-sectional study, we identified this allele gene among 46 of the adults with T2DM, which were consist of 23 active smokers and 23 passive smokers. The CYP2A6*4 allele gene identification has done using polymerase chain reaction (PCR) methods. The CYP2A6*4 allele frequency was analyzed to describe the distribution of this allele among the participants. This study supports the hypothesis that smoking, including cigarette smoke, was an environmentally modifiable risk factor for developing T2DM. Based on our result, the allele frequency among the participants was 42.39%. A high frequency of the CYP2A4 allele gene among the participants was indicating that the CYP2A4 allele gene was also the other risk factor in developing T2DM.

POLYMORPHISM OF CYTOCHROME P450 2A6 (CYP2A6*1 AND CYP2A6*4) AMONG JAVANESE INDONESIAN SMOKER AND NON SMOKER Christine Patramurti; Sugiyanto .; Arief Nurrochmad; Sudibyo Martono
Indonesian Journal of Pharmacy Vol 26 No 1, 2015
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Cytochrome P450 2A6 (CYP2A6) is the principal enzyme involved in the metabolic activation of tobacco-specific nitrosamines to their ultimate carcinogenic forms and metabolism of nicotine. The present study was developed to investigate the genetic polymorphism of CYP2A6 in Javanese Indonesian subjects carrying the CYP2A6*1 allele and the CYP2A6*4. The whole gene deletion of CYP2A6 (CYP2A6*4) may inhibit smokers from giving up smoking, but appears to function as a protective factor against to some cancer. However, the investigation of these allele, a major functional polymorphisms common in Asian populations, have not been reported among Javanese Indonesian population. A single polymerase chain reaction-restriction fragment length polymorphism was used to resolve the genotypes into CYP2A6*1 (wild type) and CYP2A6*4 (CYP2A6del). The sample studied consisted of 100 healthy subject that consist of 50 non smokers and 50 smoker from Javanese Indonesian population. The allele frequencies of *1 (wild type) and *4, were 47.5 and 52.5%, respectively. When the two allel were considered simultaneously, among the non-smokers, 45% were genotyped for CYP2A6*1/*4 and 5% were genotyped for CYP2A6*4/*4; on the other hand all of the smoker were genotyped for CYP2A6*1/*4 and there was no homozygote of wild type. Based on the data collected, it could be concluded that the polymorphism of CYP2A6 were detected in among Javanese population sample study and the allele frequencies of CYP2A6*4 were high.Key word: Polymorphism, CYP2A6*1, CYP2A6*4, Javanese Indonesian

ASSOCIATION BETWEEN SMOKING BEHAVIOUR AND GLYCOHEMOGLOBINE LEVELS AMONG ADULT JAVANESE INDONESIAN SMOKERS Christine Patramurti; Fenty Fenty
Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community) Vol 17, No 2 (2020)
Publisher : Sanata Dharma University

Nicotine, the active compound in cigarettes, can cause impaired glucose metabolism byincreasing insulin resistance as well as decreasing insulin secretion in ? cell pancreas. Thiscondition can increase the risk of type 2 diabetes in human. This study aims to evaluate the effectof smoking behaviour, determined by Cigarette per Day (CPD) and smoking duration, onglychohemoglobine (HbA1c) levels of Javanese Indonesian smokers. 30 smokers were studiedconsisting of 7 smokers with 10 CPD, 19 smokers with 11-20 CPD and 4 smokers with 21-30CPD. They had been smoking for more than 10 years. The whole blood sample was used toexamine the HbA1c levels. The HbA1c levels were tested at Bethesda Hospital's cliniclaboratories using Architect 600 instrument. The results showed that CPD and smoking durationsignificantly influenced HbA1c, in which F count was F table (370.541 3.354) withsignificance 0.05 (2.35. 10-20 0.05) and multiple correlation coefficient (R) of 0.982.Therefore, based on this research finding, it was concluded that longer smoking duration andhigher CPD caused higher smokers HbA1c level.

Studi Genotipe Sitokrom P450 2A6 Alel CYP2A6*4 dan CYP2A6*9 pada Subyek Uji Perokok Suku Jawa Indonesia CHRISTINE PATRAMURTI; FENTY FENTY
JURNAL ILMU KEFARMASIAN INDONESIA Vol 15 No 1 (2017): JIFI
Publisher : Fakultas Farmasi Universitas Pancasila

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (273.928 KB)

CYP2A6 belongs to the CYP2 family of P450 cytochromes were highly polimorphy. CYP2A6*1 (wild type) was an active allele, CYP2A6*9 was agen decreased allele and the CYP2A6*4 was an inactive allele. By using the polymerase chain reaction technique (PCR), the CYP2A6 polymorphism was studied among Javanese Indonesian smokers. In the process of genotyping the CYP2A6*9 allele, some subjects who had been genotyped as CYP2A6*1/*4 in our previous studies were regenotyped as CYP2A6*9 in this study. The primer forward 2A6*9S and the primer reverse 2A6*9AS-wild type were used in these study. The Promega Go Taq Green Master Mix reagent were used to amplifl y the allele CYP2A6*1 in the positions at -395 to -28 of the CYP2A6 gene. The sample studied consisted of 20 smokers with Cigarrete per-Day (CPD) <10 and 13 smoker with CPD 11-20 from Javanese Indonesian population. In theses research, the subjects had been genotyped as CYP2A6*1/*4 in our previous studies. The allele frequencies of CYP2A6*1, CYP2A6*4, and CYP2A6*9 were 48.5%, 48.5%, and 3%, respectively. When these allele were considered simultaneously, among the subject, 63.9% were genotyped for CYP2A6*1/*4 and 6.1% were genotyped for CYP2A6*1/*4/*9. Based on the data collected, it could be concluded that the polymorphism of CYP2A6 among Javanese population sample study was not aff ected on smoking behavior.

Metode Kromatografi Cair Kinerja Tinggi Menggunakan Kolom Oktil Silika Fully Endcapped Residual Silanol pada Pemisahan Kotinin dan 3-Hidroksikotinin dalam Sampel Urin CHRISTINE PATRAMURTI; SUDIBYO MARTONO; SUGIYANTO SUGIYANTO; ARIEF NURROCHMAD
JURNAL ILMU KEFARMASIAN INDONESIA Vol 12 No 1 (2014): JIFI
Publisher : Fakultas Farmasi Universitas Pancasila

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (651.382 KB)

Cotinine (COT) and 3-hydroxycotinine (3-HCOT) are nicotine metabolite excreted in urine. Mediated by the enzyme cytochrome P450 2A6 (CYP 2A6), nicotine will be metabolized to COT and 3-HCOT. The activity of CYP 2A6 can be predicted from the ratio 3-HCOT to the COT, therefore the ratio of 3-HCOT and COT can be used as phenotyping and polymorphism studies of the enzyme. In this study, isolation COT and 3-HCOT of urine samples was carried out by liquid-liquid back extraction. Simultaneous analysis of COT and 3-HCOT using High Performance liquid Chromatography (HPLC) was performed by a reversed-phase octyl silica column (C8; Shimadzu 250 × 4.6 mm, 5 μm) fully endcapped residual silanol. The internal standard solution (SI) was acetanilide. The mobile phase which separate COT, 3-HCOT and SI was methanol : ammonium acetate 5 mM (50:50) at a flow rate 0.8 mL/min. Retention time (tR) of the three compounds was less than 10 minutes, with peak tailing factor (tf) was less than 2. The resolution (Rs) 3-HCOT to COT was 2.67, while the Rs COT to SI was 8.836.

Genetic Polymorphism Cytochrome P4502a6 Allel *4 And *9: Studi On Glycohemoglobine Level Among Javanese Indonesian Smokers Patramurti, Christine; Fenty,
Pharmaceutical Sciences and Research Vol. 6, No. 2
Publisher : UI Scholars Hub

Show Abstract | Download Original | Original Source | Check in Google Scholar

Nicotine, the active compound in cigarettes, was considered as the risk factor for type 2 diabetes mellitus (T2DM). In the human body, nicotine would be metabolized by the enzyme cytochrome P450 2A6 (CYP2A6). CYP2A6 was known to be highly polymorphic. The active form of this gene was CYP2A6 *1, while the CYP2A6 *4 and CYP2A *9 alleles were the inactive alleles. The presence of this inactive allele caused the decreased activity of CYP2A6 so that it would affect the level of nicotine in the blood and would eventually cause an increased blood sugar levels. This study aimed to determine the effect of CYP2A6 polymorphism on glycohemoglobine levels among Javanese smokers. The blood sugar levels were measured by hemoglobin A1c (HbA1c). In this study, 33 active smokers involved in the study were identified as slow metabolizers, by which 63.9% of all test participants had CYP2A6 *1/*4 genotype and as many as 6.1% of the test participants had the CYP2A6 *1/*4/*9. The HbA1c levels among the participants have been analyzed, 28 participants were in normal range (4.83-5.56%); 4 participants were identified in prediabetes condition (5.70% - 5.97%) and 1 participant was in diabetes with HbA1c level was 7.16%. This condition indicates that the presence of CYP2A6 *4 and *9 alleles will affect HbA1c levels which can eventually lead to T2DM disease.

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