Novel single nucleotide polymorphisms (SNPs) of CYP2W1 gene in Chinese Uygur and Han populations

Qi, Guangzhao; Wang, Xin; Miao, Xiaojie; Yin, Sheng-Ju; Ren, Hong; Lou, Ya-Qing; Zhang, Guoliang

doi:10.1016/j.dmpk.2015.11.003

Cited by 6 publications

(2 citation statements)

References 14 publications

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“…Five known alleles (CYP2W1*1A, *1B,*2, *4, and *6) were identified in this study, whereas CYP2W1*3 and *5 were not found. The frequencies of these alleles in the Chinese Han and Uighur populations obtained in this study were in agreement with those reported in a recent study (Qi et al,2015) (Supplemental Table 3). Moreover, CYP2W1*1A and *1B presented with comparable frequencies in the studied Han Chinese Population Genetic Study of the CYP2W1 Gene population and the Japanese population, whereas CYP*2, *4, and *6 demonstrated varied frequencies among these two populations (Hanzawa et al, 2008) (Supplemental Table 3).…”

Section: Discussionsupporting

confidence: 92%

Identification of Genetic Polymorphisms of CYP2W1 in the Three Main Chinese Ethnicities: Han, Tibetan, and Uighur

Kang

et al. 2016

Drug Metabolism and Disposition

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CYP2W1 is an orphan member of the cytochrome P450 superfamily. Recently, CYP2W1 has gained great research interest because of its unknown enzymatic function and tumor-specific expression property. This study aims to investigate the genetic polymorphisms of the CYP2W1 gene in Chinese populations and explore the functions of the detected variants. All of the nine exons and exon-intron junction regions of the CYP2W1 gene were sequenced in 150 Chinese subjects, including 50 Han Chinese, 50 Tibetans, and 50 Uighurs. A total of 26 genetic variants were identified in this study, and 19 polymorphisms were detected in each population. Frequency comparison between populations showed that nine variants exhibited significantly different allelic distributions. A total of 12 different haplotypes were inferred from 150 samples by using the genotype data of nine exonic variants found in this study. CYP2W1*1A, *1B, *2, *4, and *6 were detected as the main alleles/haplotypes. Moreover, one, three, and two ethnically specific haplotypes were observed in the Han, Tibetan, and Uighur samples, respectively. Then, the effects of four detected missense mutations (Ala181Thr, Gly376Ser, Val432Ile, and Pro488Leu) on the CYP2W1 protein function were predicted using three in silico tools: Polymorphism Phenotyping v2, Sorts Intolerant from Tolerant, and MutationTaster. The results showed that Gly376Ser and Pro488Leu may have deleterious effects. In summary, this study showed that the genetic pattern of CYP2W1 is interethnically different among the three Chinese populations, and this finding can extend our understanding of population genetics of CYP2W1 in the Chinese population.

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Section: Discussionsupporting

confidence: 92%

Identification of Genetic Polymorphisms of CYP2W1 in the Three Main Chinese Ethnicities: Han, Tibetan, and Uighur

Kang

et al. 2016

Drug Metabolism and Disposition

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“…Four of them had amino acid substitutions that might affect CYP2W1 function according to computational prediction. The allelic frequencies are different among Chinese Han, Uygur and Caucasians, for example 2.9%, 5.2%, 9.1% for CYP2W1*2 and 0%, 0%, 33.1% for CYP2W1*3, respectively (Hanzawa et al, 2008;Qi et al, 2015).…”

Section: Polymorphismmentioning

confidence: 98%

The CYP2W1 enzyme: regulation, properties and activation of prodrugs

Guo

Johansson

Mkrtchian

et al. 2016

Drug Metabolism Reviews

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CYP2W1 is expressed in the course of development of the gastrointestinal tract, silenced after birth in intestine and colon by epigenetic modifications, but activated following demethylation in colorectal cancer (CRC). The expression levels in CRC positively correlate with the degree of malignancy, are higher in metastases and are predictive of colon cancer survival. The CYP2W1 transcripts have been detected also in hepatocellular carcinoma, adrenocortical carcinoma, childhood rhabdomyosarcoma and breast cancer; however, here the protein expression remains to be confirmed. The CYP2W1 enzyme has an inverted orientation in the endoplasmic reticulum membrane, as compared to other cytochrome P450s and its immediate electron donor is unknown. Several lipid ligands have been proposed as endogenous substrates, among which retinol derivatives appear to have the highest affinities. However, the role of CYP2W1 in the endogenous and tumor localized metabolism of retinol derivatives has yet to be clarified. Indolines constitute high affinity exogenous compounds and specific chloromethylindolines have been shown to be activated by CYP2W1 into cytotoxic products in vitro and also in vivo, inhibiting the growth of human colon tumors in a mouse xenograft model. The CRC specific localization of CYP2W1 and its effective prodrug activation makes it a very promising target for future development of cancer therapeutics.

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Genetic variation of cytochrome P450 in Uyghur Chinese population

Zhang

2018

Drug Metabolism and Pharmacokinetics

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Novel single nucleotide polymorphisms (SNPs) of CYP2W1 gene in Chinese Uygur and Han populations

Cited by 6 publications

References 14 publications

Identification of Genetic Polymorphisms of CYP2W1 in the Three Main Chinese Ethnicities: Han, Tibetan, and Uighur

Identification of Genetic Polymorphisms of CYP2W1 in the Three Main Chinese Ethnicities: Han, Tibetan, and Uighur

The CYP2W1 enzyme: regulation, properties and activation of prodrugs

Genetic variation of cytochrome P450 in Uyghur Chinese population

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