Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations

Abstract

CYP2C9 is the major P450 2C enzyme in human liver and contributes to the metabolism of a number of clinically important substrate drugs. This polymorphically expressed enzyme has been studied in Caucasian, Asian, and to some extent in African American populations, but little is known about the genetic variation in Native American populations. We therefore determined the 2C9*2 (Arg144Cys) and 2C9*3 (Ile359Leu) allele frequencies in 153 Native Canadian Indian (CNI) and 151 Inuit subjects by PCR-RFLP techniques. We also present genotyping data for two reference populations, 325 Caucasian (white North American) and 102 Chinese subjects. Genotyping analysis did not reveal any 2C9*4 alleles in the CNI, Inuit, Caucasian, or Chinese individuals. The 2C9*2 allele appears to be absent in Chinese and Inuit populations, but was present in CNI and Caucasian subjects at frequencies of 0.03 and 0.08-0.15, respectively. The 2C9*3 allele was not detected in the Inuit group, but occured in the CNI group (f = 0.06) at a frequency comparable to that of other ethnic groups. This group of Inuit individuals are the first population in which no 2C9*2 or *3 alleles have been detected so far. Therefore, these alleles may be extremely rare or absent, and unless other novel polymorphisms exist in this Inuit group one would not anticipate any CYP2C9 poor metabolizer subjects among this population.

Cytochrome P450 Enzyme Polymorphism Frequency in Indigenous and Native American Populations: A Systematic Review

“…By contrast, CYP2C9 * 2 and CYP2C9 * 3 appear to be more prevalent in European and American populations [19, 20]. In cohorts of Inuits and Native Canadian Indians (CNI), Gaedigk et al[21]noted the absence of the CYP2C9 * 2 allele in the Inuit population, but its presence in CNI at a frequency of 3.0%. The CYP2C9 * 3 allele occurred in the CNI group at a frequency of 6.0%, but was absent in the Inuit group.…”

Investigations of genetic polymorphisms related to Behcet\s disease in Turkish population

“…Normal aktiviteli (yabanıl tip) allel CYP2C19*1 ve CYP2C9'da nokta mutasyonla oluşan iki allelik varyant olan CYP2C9*2 ve CYP2C9*3 varlığı bildirilmiştir. Bu mutasyon allelerinin enzim kapasitesi hızlı metabolizör olarak da adlandırılan yabanıl tipe göre düşüktür (106). Türk popülasyonunda CYP2C9*2 ve CYP2C9*3 polimorfizminin BH ile ilişkisi araştırılmış ve bir anlamlılık olmadığı kaydedilmiştir (107).…”

Prevalence of CYP2C9 polymorphisms in the south of Europe

“…Population diversity CYP2C9*2 and *3 allele frequencies were compared among the sampled populations and also among data previously published for 12 European populations scattered all over the continent from the United Kingdom, 17 Holland, 18 France, 16 Germany, 19 Hungary, 20 Italy, 21 Sweden, 22 Turkey, 12 Belgium, 13 Iran, 14 Spain 11 and the Europeans from the United States of America 23 (Table 4). No significant differences were observed among our five samples in any of the CYP2C9 variants.…”

“…[11][12][13][14][15][16][17][18][19][20][21][22][23] Here we present a descriptive study of the prevalence of the most relevant CYP2C9 polymorphisms, CYP2C9*1 (wild type), CYP2C9*2 and CYP2C9*3, in population samples from both Spain (Basque Country, Catalonia, Central Spain and Galicia) and northern Italy (Verona) summing up a total of 1240 individuals. We also compared the allele frequencies on our population samples with those previously published for other European populations.…”

“…We also compared the allele frequencies on our population samples with those previously published for other European populations. On the other hand, various single nucleotide polymorphisms (SNPs) were identified in the flanking region of the CYP2C9 gene, 23 which appear to influence CYP2C9 activity. However, the impact of these non-coding SNPs on CYP2C9 activity in vivo and in therapeutics still has to be evaluated in Caucasians.…”