Cytochrome P450, Subfamily IIC, Polypeptide 9

Alternative Names

  • CYP2C9

Associated Diseases

Coumarin Resistance
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OMIM Number

601130

NCBI Gene ID

1559

Uniprot ID

P11712

Length

51,434 bases

No. of Exons

9

No. of isoforms

2

Protein Name

Cytochrome P450 2C9

Molecular Mass

55628 Da

Amino Acid Count

490

Genomic Location

chr10:94,938,658-94,990,091

Gene Map Locus
10q23.33

Description

CYP2C9 encodes a monooxygenase enzyme, part of the cytrochrome P450 superfamily, and is important for catalyzing drug metabolism as well as the synthesis of lipoproteins, peptides, and lipids. 

Epidemiology in the Arab World

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Variant NameCountryGenomic LocationClinvar Clinical SignificanceCTGA Clinical Significance Condition(s)HGVS ExpressionsdbSNPClinvar
NM_000771.3:c.430C>TLebanon; United Arab E...NC_000010.11:g.94942290C>TDrug Response, Likely BenignDrug ResponseCoumarin ResistanceNG_008385.1:g.8633C>T; NM_000771.3:c.430C>T; NP_000762.2:p.Arg144Cys17998538409
NM_000771.3:c.449G>CUnited Arab EmiratesNC_000010.11:g.94942309G>CNG_008385.1:g.8652G>C; NM_000771.3:c.449G>C; NP_000762.2:p.Arg150Pro7900194
NM_000771.4:c.1075A>CLebanon; United Arab E...NC_000010.11:g.94981296A>CDrug ResponseDrug ResponseCoumarin ResistanceNG_008385.1:g.47639A>C; NM_000771.4:c.1075A>C; NP_000762.2:p.Ile359Leu10579108408

Other Reports

Oman

Pathare et al. (2012) carried out a study of genetic polymorphisms of the CYP2C9, CYP4F2, and VKORC1 loci together for 240 (180 males and 60 females) healthy Omani participants. Using direct sequencing for exons 3 and 7 of CYP2C gene for 220 samples, the frequency for combined CYP2C9 mutant allele (CYP2C9 *2, *3 and *8) in Omanis was 0.16; the homozygous and compound heterozygous state was about 4% among Omanis, while the heterozygous state was 24%. The frequency of warfarin-sensitive homozygous and compound heterozygous was of intermediate value between Caucasians and African Americans/Asians. While CYP2C9 (*4, *5 and *9) alleles were not found in Omani participants. Two of the patients were found to have warfarin-sensitive genotype for both CYP2C9 and VKORC1 loci together (1.2%).

Tanira et al. (2007) correlated CYP2C9 genotypes with warfarin dosage in 189 Omani patients on Warfarin. Of these, 13% and 6% patients were heterozygous for the CYP2C9*2 and CYP2C9*3 alleles, respectively, while 1% were homozygous for the CYP2C9*2 allele. This was the first time CYP2C9*2 homozygosity was reported in an Asian or African population. The frequency of CYP2C9*2 and CYP2C9*3 alleles were calculated at 0.079 and 0.029, respectively. The mean maintenance dose of warfarin for those with wildtype alleles was found to be higher than the mean maintenance dose in patients with variant alleles.

Saudi Arabia

Mirghani et al. (2011) studied a cohort of 192 healthy unrelated Saudi subjects (82 men and 110 women) to investigate the frequencies of the major variants of the CYP2C9 in Saudi Arabians.  The subjects were assumed healthy by their medical history.  The average age of the subjects was around 32-years. The determinations of *2 and *3 cover more than 98% of several populations.  For this reason, only these two major variants of CYP2C9 in the Saudi population were analyzed.  The most common genotype was *1*1 with a frequency of 64.1% (n = 123).  The rare homozygous mutated genotypes were between 1.6% and 2.1%.  The frequencies of heterozygous subjects were 17.2% and 13.0% for the *2 and *3 variants, respectively. Accumulating data demonstrate the decreased catalytic activity of the enzyme encoded by *2 or *3 for different drug substrates of CYP2C9.  The authors concluded that in Saudi Arabians, the frequencies of the major CYP2C9 variants, *2 and *3, are similar to those of Caucasians and significantly higher than those of Orientals and Africans.

Sudan

Shrif et al. (2011) studied the possible association between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in 203 Sudanese warfarin-treated patients. Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8 mg/day, P?

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