CYP2C8 polymorphism among the Portuguese

Abstract

Cytochrome P450 2C8 (CYP2C8) is a polymorphic phase I drug-metabolising enzyme involved in the metabolism of a wide variety of xenobiotics, as well as a proposed player in the regulation of vascular tone. Polymorphisms in this gene may have an impact on the metabolism of therapeutic drugs such as paclitaxel and verapamil. In this report we have determined the frequencies of the main non-synonymous CYP2C8 alleles, 805A>T (CYP2C8*2), 416G>A/1196A>G (CYP2C8*3) and 792C>G (CYP2C8*4) in a sample representative of Portuguese Caucasians. The allelic frequencies determined were 1.2%, 19.8%, and 6.4% for CYP2C8*2, CYP2C8*3, and CYP2C*4, respectively. The observed CYP2C8*3 prevalence is significantly different from the frequencies previously reported in North European populations.

Absence of the human CYP2C8*3 allele in Ugandan children exposed to Plasmodium falciparum malaria

“…While CYP2C8*2 is found to be present in Africans and in African-Americans at relatively high frequency (9.9-24.2% allele frequency, Alessandrini et al, 2013) CYP2C8*3 is more prevalent in Caucasian populations (5.9-20% allele frequency, Bahadur et al, 2002;Henningsson et al, 2005;Cavaco et al, 2006;Weise et al, 2010;Pechandova et al, 2012) and almost absent in Africans except those from Zanzibar (Cavaco et al, 2005). Our results confirm the previous findings about the CYP2C8*3 allele.…”

Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

“…The allele is also relatively common in the mixed Brazilian population with a frequency of 0.06, New York area Hispanic population with a frequency of 0.02, and North and South Indian populations, with frequencies of 0.03 and 0.01, respectively Martis et al, 2013;Minhas et al, 2013;Arun Kumar et al, 2015). The CYP2C8*2 allele is very rare or absent in East Asian and European populations, with the exception of an allele frequency of 0.01 in a Portuguese European sample (Nakajima et al, 2003;Muthiah et al, 2005;Cavaco et al, 2006;Pechandova et al, 2012;Vargens et al, 2012;Martis et al, 2013;Wu et al, 2013). The CYP2C8*3 allele is a haplotype consisting of two nonsynonymous variants (c.416G.A, p.Arg139Lys and c.1196A.G, p.Lys399Arg), which appear to be in a complete or nearly complete linkage disequilibrium in all investigated populations (1000 Genomes Project Consortium, 2012).…”

“…In European populations, the allele frequency of CYP2C8*3 ranges from 0.069 in Faroe Islanders to 0.198 in a Portuguese population, with an apparent north-to-south cline from lower to higher frequencies (Fig. 6;Yasar et al, 2002;Halling et al, 2005;Cavaco et al, 2006;Speed et al, 2009;1000Genomes Project Consortium, 2012Pechandova et al, 2012;Suarez-Kurtz et al, 2012). The allele is also quite common in European American and North American Hispanic populations, with frequencies of 0.09 and 0.08, respectively (Martis et al, 2013).…”

“…The CYP2C8*4 (c.792C.G, p.Ile264Met) allele has its highest frequencies in European populations, with the allele frequency ranging from 0.04 in a Spanish population to 0.07 in the Irish (Cavaco et al, 2006;Speed et al, 2009;1000Genomes Project Consortium, 2012Pechandova et al, 2012). Its frequency was 0.03 in a European American population and a mixed Brazilian population Martis et al, 2013).…”

Pharmacokinetic studies of enantiomers of ibuprofen and its chiral metabolites in humans with different variants of genes coding CYP2C8 and CYP2C9 isoenzymes

“…However, data regarding CYP2C8 gene polymorphism are scarce because most of the mutations seem to occur at low frequencies (Bahadur et al 2002). Among Caucasians CYP2C8*3 and CYP2C8*4 occur at frequencies of greater than 5% (Bahadur et al 2002;Cavaco et al 2006) but CYP2C8*4 does not seem to cause a significant effect on enzyme activity (Bahadur et al 2002). CYP2C8*2 and CYP2C9*5 occur among Africans and Oriental population, respectively (Dai et al 2001;Nakajima et al 2003).…”