SNP communication ANovel single nucleotide polymorphisms (SNPs) of CYP2W1 gene in Chinese Uygur and Han populations☆
Introduction
Cytochrome P450 2W1 (CYP2W1) was demonstrated to be expressed in fetal tissues, predominantly the colon, but silenced after birth and could not be detected in adult tissues [1]. However, CYP2W1 was re-expressed in some transformed tissues, like colorectal, hepatic and adrenal tumors [2], [3]. Initially, CYP2W1 was considered to be an orphan enzyme, whereas, some potential substrates of it had been found recently, such as aromatic amines [4], lysophospholipids [5] and duocarmycin analogs [6]. Promisingly CYP2W1 might be an anticancer drug target because it could metabolize some duocarmycin analogs into cytotoxic substances and subsequently inhibit the growth of cancer cells.
CYP2W1 locates on chromosome 7p22.3, spanning over 5.5 kb with nine exons. The open-reading frame is 1473-nucleotide long and encodes a 490-amino acid long polypeptide. Until now there are seven alleles of CYP2W1 (CYP2W1*1A, *1B, *2–*6) in the CYP allele nomenclature webpage (http://www.cypalleles.ki.se/cyp2w1.htm), including five non-synonymous single nucleotide polymorphisms (SNPs): 173A > C (Glu58Ala), 2008G > A (Ala181Thr), 5432G > A (Val432Ile), 5584G > C (Gln482His), and 5601C > T (Pro488Leu), and one synonymous SNP: 166C > T [7]. Association of CYP2W1 variants with colorectal cancer risk had been investigated in Caucasians [8], [9]. However, genetic polymorphisms of CYP2W1 in Chinese had not been reported yet.
Until recently the systematic investigation of genetic variants of CYP2W1 had only been performed in one Japanese population. Besides a Han majority group, Chinese Uygur is a larger minority group with the population of approximately 10.07 million people (2010 census), who reside in the Silk Road of northwestern China with genetic admixture between Orientals and Caucasians and our previous studies showed that intermediate allele frequencies of MDR1, CYP3A5, CYP2C19 and CYP2E1 were observed in Chinese Uygur between Han and Caucasians populations [10], [11]. To investigate the genetic polymorphism of CYP2W1 among Chinese, all the nine exons and exon–intron junctions were sequenced in 385 healthy Chinese subjects (including 223 Han and 162 Uygur).
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Materials and methods
Three hundred and eighty-five unrelated mainland Chinese healthy volunteers, including 223 Chinese Han and 162 Chinese Uygur, were recruited for the present study. Each subject had the same ethnic origin for at least three generations, i.e., on both mothers' and fathers' sides, also the status of the grandparents. The present study protocol was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Beijing University, Beijing, China. Written informed
Results and discussion
Ten novel SNPs were found as follows:
- 1)
SNP: 150901Zhang/Qi001; GENE NAME: CYP2W1; ACCESSION NUMBER: NC_000007.14; LENGTH: 25 bases; 5′-TCGTCGGGAACCT/CGCACTTGCTGCG-3′.
- 2)
SNP: 150901Zhang/Qi002; GENE NAME: CYP2W1; ACCESSION NUMBER: NC_000007.14; LENGTH: 25 bases; 5′-CTGGGCCTGTCGG/TCTGCCTGCTCAG-3′.
- 3)
SNP: 150901Zhang/Qi003; GENE NAME: CYP2W1; ACCESSION NUMBER: NC_000007.14; LENGTH: 25 bases; 5′-CCCCCCTCGGCCC/GTCAGGTGTTCAA-3′.
- 4)
SNP: 150901Zhang/Qi004; GENE NAME: CYP2W1; ACCESSION NUMBER: NC_000007.14;
Conflict of interest
No conflict of interests have been declared.
Acknowledgments
We are grateful to Mr. An-ping Zhu, Ms. Zhen Wang and Ms. Ping Zhang (The Central University for Nationalities, P. R. China) for their assistance in subject recruitment. This study was supported by National Natural Science Foundation of China (Grants No.30973585 91029747 and 81473276), and the Beijing University Center for Human Disease Genomics (Grant No 2000A-1).
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Genetic variation of cytochrome P450 in Uyghur Chinese population
2018, Drug Metabolism and PharmacokineticsCitation Excerpt :Here we review the studies of genetic variations in Uyghur Chinese of fifteen CYP450 genes including CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP2W1, CYP3A4, CYP3A5, CYP4A11, and CYP17A1, which totally covered 277 variants. We collected 8 studies using Sanger's sequencing method investigating the 5′ flanking region, all exons, introns and 3′ flanking region of CYP1A2 [6], CYP2C9 [7], CYP2C19 [8], CYP2D6 [9], CYP2W1 [10,11], CYP3A4 [12] and CYP3A5 [13] in Uyghur Chinese, and 8 studies investigating several variant alleles of CYP1A1 [14], CYP2A6 [15], CYP2B6 [16], CYP2C8 [17], CYP2E1 [18], CYP2J2 [19], CYP4A11 [20], and CYP17A1 [21] in Uyghur Chinese (Table 1). We also collected the data of 277 variants covered in our study in two extensive population sequencing projects, the International HapMap Project (Hap-Map) and the 1000 Genomes Project (Supplementary data 1).
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2019, Journal of Xinxiang Medical UniversityIdentification of genetic polymorphisms of CYP2W1 in the three main Chinese ethnicities: Han, Tibetan, and Uighur
2016, Drug Metabolism and Disposition
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On September 1, 2015, the variation was not found on the CYP allele nomenclature webpage (http://www.cypalleles.ki.se/cyp2w1.htm), the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/SNP/), or the PharmGKB (http://www.pharmgkb.org/) database.