Genetic polymorphism of CYP2A6 in the German population

Bourian, M.; Gullstén, Harriet; Legrum, Wolfgang

doi:10.1016/s0300-483x(99)00199-7

Cited by 19 publications

(11 citation statements)

References 22 publications

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“…Similar results were obtained in another study on Brazilian individuals (30), which found allele frequencies of 0.38 and 0.24 for CYP2A6*1B and 0.02 and 0.01 for CYP2A6*2 among white and non-white Brazilians, respectively. The results obtained for the population from Rio de Janeiro are similar to those obtained for Europeans and North Americans, whose allelic frequencies are about 0.30 for CYP2A6*1B and 0.01-0.03 for CYP2A6*2 among Caucasians (11,28,31,32). We did not detect the presence of the CYP2A6*5 allele in the population studied.…”

Section: Resultssupporting

confidence: 83%

<a name="home"></a>CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro

Rossini

Lima

Rapozo

et al. 2006

Braz J Med Biol Res

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Cytochrome P450 (CYP) is a superfamily of enzymes involved in the metabolism of endogenous compounds and xenobiotics. CYP2A6 catalyzes the oxidation of nicotine and the activation of carcinogens such as aflatoxin B1 and nitrosamines. CYP2E1 metabolizes ethanol and other low-molecular weight compounds and can also activate nitrosamines. The CYP2A6 and CYP2E1 genes are polymorphic, altering their catalytic activities and susceptibility to cancer and other diseases. A number of polymorphisms described are ethnic-dependent. In the present study, we determined the genotype and allele frequencies of the main CYP2A6 and CYP2E1 polymorphisms in a group of 289 volunteers recruited at the Central Laboratory of Hospital Universitário Pedro Ernesto. They had been residing in the city of Rio de Janeiro for at least 6 months and were divided into two groups according to skin color (white and non-white). The alleles were determined by allele specific PCR (CYP2A6 ) or by PCR-RFLP (CYP2E1). The frequencies of the CYP2A6*1B and CYP2A6*2 alleles were 0.29 and 0.02 for white individuals and 0.24 and 0.01 for non-white individuals, respectively. The CYP2A6*5 allele was not found in the population studied. Regarding the CYP2E1*5B allele, we found a frequency of 0.07 in white individuals, which was statistically different (P < 0.05) from that present in non-white individuals (0.03). CYP2E1*6 allele frequency was the same (0.08) in both groups. The frequencies of CYP2A6*1B, CYP2A6*2 and CYP2E1*6 alleles in Brazilians are similar to those found in Caucasians and African-Americans, but the frequency of the CYP2E1*5B allele is higher in Brazilians.

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Section: Resultssupporting

confidence: 83%

<a name="home"></a>CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro

Rossini

Lima

Rapozo

et al. 2006

Braz J Med Biol Res

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“…[10,11,15,22] The allele frequencies of CYP2A6*2 were reported to be 1.1% in Swedes, [25] 1.4% in Finns, [25] 3.0% in Spaniards, [25] and 2.3% in Germans. [26] The allele frequencies of CYP2A6*3 have been reported to be 0% in Spaniards, [15] 1.4% in Germans, [26] and 0% in Caucasians. [27] It has been described that whether this allele actually exists is uncertain.…”

Section: Ethnic Differences In Allele Frequency Of Cyp2a6 Genementioning

confidence: 99%

Interindividual Differences in Nicotine Metabolism and Genetic Polymorphisms of Human Cyp2a6

Nakajima

Kuroiwa

Yokoi

2002

Drug Metabolism Reviews

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Nicotine is widely consumed throughout the world, and exerts a number of physiological effects. After nicotine is absorbed through the lungs by cigarette smoking, it undergoes extensive metabolism in humans. Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. CYP2A6 can metabolize some pharmaceutical agents such as halothane, valproic acid, and fadrozole, and activate tobacco-specific nitrosamines. There are large interindividual differences in nicotine metabolism, and it has been found that the interindividual differences are attributed to the genetic polymorphisms of CYP2A6 gene. This review describes the techniques for determination of in vivo nicotine metabolism, characteristics of each human CYP2A6 alleles, and ethnic differences. The relationship between CYP2A6 genetic polymorphism and potency of nicotine metabolism, smoking behavior, and cancer risk are extensively reviewed. Finally, the usefulness of nicotine metabolism for phenotyping of CYP2A6 in individuals and implication of the significance of CYP2A6 genetic polymorphism in a clinical perspective are discussed.

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“…Further studies of other ethnic populations should be made, because marked inter-ethnic differences in the distribution of CYP2A6 polymorphisms have been reported (10,16,(25)(26)(27).…”

Section: The Cyp2a6*6 Polymorphism Inactivates Enzymatic Activitymentioning

confidence: 99%

CYP2A6*6, a Novel Polymorphism in Cytochrome P450 2A6, Has a Single Amino Acid Substitution (R128Q) That Inactivates Enzymatic Activity

Kitagawa

Kunugita

Kitagawa

et al. 2001

Journal of Biological Chemistry

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By using the polymerase chain reaction technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP), a novel polymorphism of CYP2A6, CYP2A6*6, was detected in 0.4% of the Japanese population. To study the enzymatic properties of the CYP2A6.6 protein with a single amino acid substitution of arginine 128 to glutamine, both this isozyme and the CYP2A6.1 protein (wild-type) were produced in insect cells using a baculovirus system. Coumarin 7-hydroxylation, which reflects CYP2A6 activity, was significantly reduced (one-eighth of normal) in cell lysate from CYP2A6*6-transfected Sf9 cells compared with that lysate from CYP2A6*1-transfected cells. To clarify the mechanism of inactivation of the CYP2A6.6 enzyme, the heme content and reduced CO difference spectrum were examined. Although CYP2A6.6 retained about onehalf the heme content of CYP2A6.1, the reduced CObound Soret peak was completely lost. These results suggest that the inactivation of CYP2A6.6 is mainly due to disordering of the holoprotein structure rather than a failure of heme incorporation.

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Genetic polymorphism of CYP2A6 in the German population

Cited by 19 publications

References 22 publications

<a name="home"></a>CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro

<a name="home"></a>CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro

Interindividual Differences in Nicotine Metabolism and Genetic Polymorphisms of Human Cyp2a6

CYP2A6*6, a Novel Polymorphism in Cytochrome P450 2A6, Has a Single Amino Acid Substitution (R128Q) That Inactivates Enzymatic Activity

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