title: Differences in CYP3A5*3 genotype distribution and combinations with other polymorphisms between Spaniards and Other Caucasian populations.
abstract: The goal of this study was to detect genotypic differences between Spaniards and other related populations regarding CYP3A4*1B, CYP3A5*3, and ABCB1 (MDR1) C3435T polymorphisms. DNA from 177 Spanish patients were analyzed for the presence of these mutations using PCR-restriction fragment length polymorphism or direct sequencing. The observed frequencies for CYP3A4*1B, CYP3A5*3, and C3435T alleles were within normal values in Caucasians (0.04, 0.91, and 0.5, respectively). However, 2.8% of the patients were homozygous for the wild-type CYP3A5*1 allele, an extremely uncommon genotype in other Caucasians. In addition, analysis of CYP3A4-3A5 haplotypes revealed the existence of 2 unusual subgroups: patients who were homozygous wild-type for both polymorphisms, and patients showing a CYP3A4*1A/*1B-CYP3A5*3/*3 genotype combination. The incidence of CYP3A5*1/*1 carriers and the occurrence of subjects combining the 2 above-mentioned unusual genotype combinations were more frequent in Spanish-Caucasians compared with American- or European-Caucasians. ABCB1 C3435T genotype frequencies were equally distributed between both single and combined CYP3A4 and 3A5 genotypes. These findings suggest that dose requirements for drugs metabolized by CYP3A and certain allele-disease association studies in white populations could show discrepancies in Spaniards.
authors.affiliation: Department of Pharmacology and Psychiatry, Medical School, and Clinical Pharmacology Unit, Infanta Cristina University Hospital, University of Extremadura, Badajoz, Spain. ggervasi@unex.es
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gervasini
authors.forename: Sonia
authors.initials: S
authors.lastname: Vizcaino
authors.forename: Carolina
authors.initials: C
authors.lastname: Gasiba
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Carrillo
authors.forename: Julio
authors.initials: J
authors.lastname: Benitez
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000483:Alleles; D044383:Black People / Q000208:ethnology / Q000235:genetics; D016009:Chi-Square Distribution; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D019450:Genes, MDR / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D011110:Polymorphism, Genetic; D013030:Spain; D044465:White People / Q000208:ethnology / Q000235:genetics*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D003577:Cytochrome P-450 Enzyme System; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C507084:Abcb1b protein, mouse