Analysis of CYP3A4 genetic polymorphisms in Han Chinese

Zhou, Qing; Yu, Xiaomin; Shu, Chen; Cai, Yuanqing; Gong, Wei; Wang, Xumin; Wang, Duen-mei; Hu, Songnian

doi:10.1038/jhg.2011.30

Cited by 40 publications

(31 citation statements)

References 68 publications

(83 reference statements)

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“…CYP3A4*1B/18 could not be found in our limited sample size due to the fact that the frequency of both alleles is only around 1% in the Asian population;28 however, the allele frequency of CYP3A5*3 (non-function variant) was observed to be comparable to that in other reports 29,30. Several studies, including one by our group, investigated the association of CYP3A5 genotype with tamoxifen clinical outcomes; no significant association was observed 27,31–35.…”

Section: Discussionmentioning

confidence: 84%

Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen

Sensorn

Sirachainan²,

Chamnanphon³

et al. 2013

PGPM

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BackgroundPharmacogenetic study of cytochrome P450 (CYP) gene CYP2D6 and tamoxifen outcomes remain controversial. Apart from CYP2D6, other drug-metabolizing enzymes and transporters also play a role in tamoxifen metabolic pathways. The aim of this study is to investigate the impact of CYP3A4/5, ABCB1, and ABCC2 polymorphisms on the risk of recurrence in Thai patients who received tamoxifen adjuvant therapy.MethodsPatients with early-stage breast cancer who received tamoxifen adjuvant therapy were recruited in this study. All six single-nucleotide polymorphisms (SNPs), including CYP3A4*1B (−392 A>G)/*18(878 T>C), CYP3A5*3(6986 G>A), ABCB1 3435 C>T, ABCC2*1C(−24 C>T), and ABCC2 68231 A>G, were genotyped using real-time polymerase chain reaction assays. The impacts of genetic variants on disease-free survival (DFS) were analyzed using the Kaplan–Meier method and Cox regression analysis.ResultsThe ABCB1 3435 C>T was found to have the highest allele frequency among other variants; however, CYP3A4*1B/*18 could not be found in this study. Patients with heterozygous ABCB1 3435 CT genotype showed significantly shorter DFS than those with homozygous 3435 CC genotype (P = 0.041). In contrast, patients who carried homozygous 3435 TT genotype showed no difference in DFS from wild-type 3435 CC patients. Cox regression analysis showed that the relative risk of recurrence was increased by five times (P = 0.043; hazard ratio = 5.11; 95% confidence interval: 1.05–24.74) in those patients carrying ABCB1 3435 CT genotype compared to those with ABCB1 3435 CC.ConclusionABCB1 3435 C>T is likely to have a clinically significant impact on recurrence risk in Thai patients with breast cancer who receive tamoxifen adjuvant therapy.

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Section: Discussionmentioning

confidence: 84%

Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen

Sensorn

Sirachainan²,

Chamnanphon³

et al. 2013

PGPM

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“…Han Chinese constitutes 92% of the population of mainland China and ~19% of the entire global human population (Zhou et al. ). To date, no systematic analysis of the FMR1 CGG repeat patterns and flanking haplotypes has been performed on such a large population, and limited studies have been conducted in Chinese fragile X population.…”

Section: Discussionmentioning

confidence: 99%

“…; Zhou et al. ). The CGG repeat patterns and distribution for FRAXAC2 have not yet been investigated in such a large population.…”

Section: Introductionmentioning

confidence: 98%

Distribution of fragile X mental retardation 1 CGG repeat and flanking haplotypes in a large Chinese population

Huang

Xia

Luo

et al. 2014

Molec Gen & Gen Med

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Fragile X syndrome is mainly caused by a CGG repeat expansion within the 5′ UTR of the fragile X mental retardation 1 (FMR1) gene. Previous analyses of the FMR1 CGG repeat patterns and flanking haplotypes in Caucasians and African Americans have identified several factors that may influence repeat instability. However, the CGG repeat patterns and distribution for FRAXAC2 have not yet been investigated in mainland Chinese. We surveyed the CGG repeat lengths in 1113 Han Chinese (534 males and 579 females), and the CGG repeat patterns of 534 males were determined by sequence analysis. We also explored the flanking haplotypes (DXS548-FRAXAC1-FRAXAC2) in 566 unaffected and 28 unrelated fragile X Chinese males. The most frequent alleles for DXS548 and FRAXAC1 were identical between our Chinese population and other Asian populations. We identified several low-abundance alleles for DXS548 and FRAXAC1 not found in previous studies in mainland Chinese and Taiwanese cohorts. The most frequent allele was (CGG)29 followed by (CGG)30, and the most frequent patterns were 9 + 9 + 9, 10 + 9 + 9, and 9 + 9 + 6 + 9, similar to those in Singaporeans. We identified only one premutation female carrier with 89 CGG repeats in the 1113 Han Chinese. A few associations between the CGG repeat patterns and flanking haplotypes were determined in this study. In general, the Chinese population had a smaller number of alleles and lower expected heterozygosity for all three STR markers and FRAXA locus when compared with Caucasians and African Americans. We identified a novel haplotype 7-3-5 + that is significantly associated with the full mutation.

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“…Moreover, CYP2C19*2 has been reported to be associated with the interindividual differences of 4‐hydroxylation of CPA and its clinical efficacy . In the Han Chinese population, the major CPA 4‐hydroxylases, CYP2B6 , CYP2C19 , and CYP3A5 , are genetic polymorphisms, whereas genetic polymorphisms are absent in CYP2C8 , CYP2C9 (minor CPA 4‐hydroxylases), and CYP3A4 (CPA N‐dechloroethylase). As far as we are aware, few studies have been done on CPA pharmacogenomics in a Chinese population or in DLBCL patients.…”

mentioning

confidence: 99%

Cytochrome P450 Genetic Variations Can Predict mRNA Expression, Cyclophosphamide 4-Hydroxylation, and Treatment Outcomes in Chinese Patients With Non-Hodgkin's Lymphoma

Shu

Chen

et al. 2017

The Journal of Clinical Pharmacology

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To investigate the impact of cytochrome P450 (CYP) genetic polymorphisms CYP2B6, CYP2C19, and CYP3A5 on mRNA expression, cyclophosphamide/4-hydroxycyclophosphamide pharmacokinetics, and treatment outcomes of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in Chinese patients with non-Hodgkin's lymphoma, 567 cases were investigated. Plasma concentrations of cyclophosphamide/4-hydroxycyclophosphamide were determined using liquid chromatography-tandem mass spectrometry and pharmacokinetic parameters calculated. The frequencies of CYP2B6*1/*29 and CYP2B6*1/*30 were 18 (3.2%) and 30 (5.3%), respectively. Liver samples with CYP2B6*29/*30, CYP2C19*2, CYP2B6*6, or CYP3A5*3 had significantly lower target mRNA expression. Samples with CYP2B6*6 and/or CYP2C19*2 had lower exposure to 4-hydroxycyclophosphamide, whereas those with CYP2B6*1G/*1H had higher exposure. Multivariate model showed that samples with CYP2C19*2 or CYP2B6 785A>raG had worse treatment response than samples with CYP3A5*3. CYP2C19*2, CYP2B6*6, CYP2B6*29, and CYP2B6*30 were protective factors for toxicity in the multivariate model. The best model for gene-gene interactions for treatment response contained CYP2C19*2, CYP2B6 785A>G, and CYP3A5*3 (cross-validation consistency [CVC], 8/10; P = .0035). The best prediction model for grade 2-4 toxicities had CYP2C19*2, CYP2B6 785A>G, and 516 G>T (CVC, 10/10; P < .0001). In previous reports, we were the first to report that the frequency of copy-number variations in CYP2B6 is higher among Chinese than among other ethnic populations. Genetic variations in CYP2B6, CYP2C19, and CYP3A5 dramatically affected the mRNA expression of proteins, the pharmacokinetics of 4-hydroxycyclophosphamide, and the R-CHOP treatment response in Chinese subjects. Patients carrying CYP3A5*3 were more likely to have a better treatment response, whereas patients with CYP2C19*2 or CYP2B6 516G>T, or CYP2B6 785A>G had higher tolerance to treatment.

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Analysis of CYP3A4 genetic polymorphisms in Han Chinese

Cited by 40 publications

References 68 publications

Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen

Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen

Distribution of fragile X mental retardation 1 CGG repeat and flanking haplotypes in a large Chinese population

Cytochrome P450 Genetic Variations Can Predict mRNA Expression, Cyclophosphamide 4-Hydroxylation, and Treatment Outcomes in Chinese Patients With Non-Hodgkin's Lymphoma

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