CYP3A5*3 and CYP3A4*1B allele distribution and genotype combinations: differences between Spaniards and Central Americans.
The aim of this study was to detect genotypic differences between three populations of healthy volunteers from Northern Spain (204 subjects), Nicaragua (120 subjects), and El Salvador (112 subjects) regarding CYP3A4*1B and CYP3A5*3 polymorphisms. No significant differences were found by comparing allelic frequencies between the two Central American populations. The CYP3A5*3 allele frequency was significantly different (P < 0.01) between Central Americans (76%) and Spaniards (91%). By contrast, CYP3A4*1B allele was more prevalent among Central Americans (12.5%) than among North Spaniards (4%) (P < 0.01). Analysis of CYP3A4-3A5 genotype combinations revealed that individuals carrying CYP3A4*1B/CYP3A5*1 were more represented in Central Americans (16.9%) than in Spaniards (5.4%), suggesting a marked linkage disequilibrium. These data are compatible with a higher CYP3A enzyme activity in Central Americans as opposed to Spaniards and other white groups, which could imply differences in dose requirements for drugs metabolized by CYP3A and should be considered in allele-disease association studies.
Department of Pharmacology, University of Zaragoza, Domingo Miral s/n, 50009 Zaragoza, Spain. bsinues@unizar.es
Blanca
B
Sinues
Jorge
J
Vicente
Ana
A
Fanlo
Patricia
P
Vasquez
Juan Carlos
JC
Medina
Esteban
E
Mayayo
Blanca
B
Conde
Izaskun
I
Arenaz
Begoña
B
Martinez-Jarreta
D000293:Adolescent; D000328:Adult; D000483:Alleles; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004544:El Salvador; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007197:Indians, Central American; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009527:Nicaragua; D011110:Polymorphism, Genetic; D013030:Spain; D044465:White People
D003577:Cytochrome P-450 Enzyme System; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human