Cloning and Tissue Distribution of a Novel Human Cytochrome P450 of the CYP3A Subfamily, CYP3A43

Westlind, Anna; Malmebo, Sarah; Johansson, Inger; Otter, Charlotta; Andersson, Tommy; Ingelman‐Sundberg, Magnus; Oscarson, Mikael

doi:10.1006/bbrc.2001.4505

Cited by 165 publications

(105 citation statements)

References 23 publications

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“…[6] CYP3A43 is also expressed at very low levels in adult livers, accounting for only 0.1-0.2% of CYP3A transcripts. [7,8] Interestingly, the hepatic expression of CYP3A5 is bimodal, with the high expressor exhibiting 10-30 fold higher CYP3A5 expression levels than the CYP3A5 lower expressor. [4,9] Kuehl et al found the causative CYP3A5*3 (g.6986A>G) genetic polymorphism at the position of intron 3, which disrupts the correct splicing of CYP3A5 transcripts to make a truncated CYP3A5 enzyme with no activity.…”

Section: Introductionmentioning

confidence: 99%

CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role

Park

Jung

Kim

2014

Transl Clin Pharmacol

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The cytochrome P450 (CYP) 3A subfamily is estimated to participate in the biotransformation of 50% of the currently prescribed drugs. Four members of the CYP3A subfamily have been identified in humans: CYP3A4, CYP3A5, CYP3A7, and CYP3A43. Initial data suggested that CYP3A5 accounts for only a small proportion of the total hepatic CYP3A in about 20% of samples, but it was later revealed that CYP3A5 represents more than 50% of the total CYP3A amount in some individuals. Several genetic variants have been described for the CYP3A5 gene, of which the CYP3A5*3 allele (gA6986G), the most common form and leading to the loss of CYP3A5 activity, has been extensively investigated in the aspect of pharmacokinetics and disease risk. This review summarized the molecular characteristics of the CYP3A5 gene, and discusses the association of the CYP3A5*3 polymorphism with disease risks such as cancer and hypertension, along with its role in the pharmacokinetics of CYP3A substrates.

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Section: Introductionmentioning

confidence: 99%

CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role

Park

Jung

Kim

2014

Transl Clin Pharmacol

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“…The CYP3A subfamily (P450 3A) consists of the 3A5 enzyme and three other isoforms, namely CYP3A4, CYP3A7 and CYP3A43, as well as two pseudogenes, CYP3AP1 and CYP3AP2 [24]. Functionally, CYP3A5 is responsible for 6% to 99% of total CYP3A activity in various populations, with negligible contributions from CYP3A43 and CYP3A7 isoforms.…”

Section: Introductionmentioning

confidence: 99%

Frequency of common CYP3A5 gene variants in healthy Polish newborn infants

Adler

Łoniewska

Parczewski

et al. 2009

Pharmacological Reports

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Abstract:Cytochrome P450 monooxygenases catalyze the metabolism of approximately 40-60% of widely used drugs with a A6986G CYP3A5 polymorphism determining expresser (A6986, *1) and reduced-expresser (*3) variants with modified drug metabolism activity. In this report, the allele frequency of CYP3A5 *1 and *3 (A6986 or G6986, respectively) was analyzed by the PCR-RFLP technique in a cohort of 200 Polish newborns from the West Pomeranian region. Of the studied group, 1% (n = 2/200) proved homozygous for the CYP3A5*1 allele, 89% (n = 178/200) for the *3 allele, and 10% (n = 20/200) were heterozygous for *1/*3. Similar frequencies were found in other Caucasian European populations. This study provides basic genetic data related to the metabolism of drugs, with a narrow therapeutic window in a Polish population.

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“…10,11 The role of CYP3A7 in the metabolism and clearance of these and many exogenous substrates to which the fetus is exposed, as well as large inter-individual differences in fetal CYP3A7 expression level 12 have led to the suggestion that differences in CYP3A7 expression and/or activity could contribute to inter-individual differences in embryonic toxicity and teratogenicity. 13 Since CYP3A43 is expressed at very low levels in several tissues, including liver, prostate, and testis, 14 it is not believed to play a substantial role in drug metabolism and has not been investigated as extensively as other members of the subfamily. However, the conversion of testosterone to less active forms by CYP3A43 raises the possibility that genetic variation at this locus could affect levels of circulating testosterone and possibly contribute to prostate cancer risk.…”

Section: Introductionmentioning

confidence: 99%

Sequence diversity and haplotype structure at the human CYP3A cluster

et al. 2005

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The four members of the human CYP3A subfamily play important roles in the clearance of xenobiotics, hormones, and environmental compounds. Many SNPs at the CYP3A locus have been characterized, with several showing large allele frequency differences across populations. In addition to the effects of CYP3A SNPs on drug metabolism, recent studies have highlighted the potential for CYP3A variation in susceptibility to several common phenotypes, including hypertension and cancer. We previously showed that the CYP3A4 and CYP3A5 genes have a strong haplotype structure at varying frequencies across ethnic groups. Here, we extend our re-sequencing survey to the remaining CYP3A genes in the same cluster, CYP3A7 and CYP3A43. Our study identified a large number of SNPs in coding and conserved noncoding sequences, several of which are common. The combined data set allows us to investigate patterns of sequence variation and linkage disequilibrium at the entire CYP3A locus for use in future association studies.

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Cloning and Tissue Distribution of a Novel Human Cytochrome P450 of the CYP3A Subfamily, CYP3A43

Cited by 165 publications

References 23 publications

CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role

CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role

Frequency of common CYP3A5 gene variants in healthy Polish newborn infants

Sequence diversity and haplotype structure at the human CYP3A cluster

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Cloning and Tissue Distribution of a Novel Human Cytochrome P450 of the CYP3A Subfamily, CYP3A43

Cited by 165 publications

References 23 publications

CYP3A5*3Polymorphism and Its Clinical Implications and Pharmacokinetic Role

CYP3A5*3Polymorphism and Its Clinical Implications and Pharmacokinetic Role

Frequency of common CYP3A5 gene variants in healthy Polish newborn infants

Sequence diversity and haplotype structure at the human CYP3A cluster

Contact Info

Product

Resources

About

CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role

CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role