Differences in CYP3A5*3 genotype distribution and combinations with other polymorphisms between Spaniards and Other Caucasian populations.
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.
Gervasini
Guillermo
G
Department of Pharmacology and Psychiatry, Medical School, and Clinical Pharmacology Unit, Infanta Cristina University Hospital, University of Extremadura, Badajoz, Spain. ggervasi@unex.es
Vizcaino
Sonia
S
Gasiba
Carolina
C
Carrillo
Juan Antonio
JA
Benitez
Julio
J
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*
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