CYP3A53A allele is associated with reduced lowering-lipid response to atorvastatin in individuals with hypercholesterolemia.
BACKGROUND
The cytochrome P450 isoenzyme 3A5 (CYP3A5) has an important role on biotransformation of xenobiotics. CYP3A5 SNPs have been associated with variations on enzyme activity that can modify the metabolism of several drugs.


METHODS
In order to evaluate the influence of CYP3A5 variants on response to lowering-cholesterol drugs, 139 individuals with hypercholesterolemia were selected. After a wash-out period of 4 weeks, individuals were treated with atorvastatin (10 mg/day/4 weeks). Genomic DNA was extracted by a salting-out procedure. CYP3A5*3C, CYP3A5*6 and CYP3A5*1D were analyzed by PCR-RFLP and DNA sequencing.


RESULTS
>Frequencies of the CYP3A5*3C and CYP3A5*1D alleles were lower in individuals of African descent (*3C: 47.8% and *1D: 55.2%) than in non-Africans (*3C: 84.9% and *1D 84.8%, p<0.01). Non-Africans carrying *3A allele (*3C and *1D combined alleles) had lower total and LDL-cholesterol response to atorvastatin than non-*3A allele carriers (p<0.05).


CONCLUSIONS
CYP3A5*3A allele is associated with reduced cholesterol-lowering response to atorvastatin in non-African individuals.
Willrich
Maria Alice V
MA
Department Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil. malicewi@usp.br
Hirata
Mario H
MH
Genvigir
Fabiana D V
FD
Arazi
Simone S
SS
Rebecchi
Ivanise M M
IM
Rodrigues
Alice C
AC
Bernik
Marcia M S
MM
Dorea
Egidio L
EL
Bertolami
Marcelo C
MC
Faludi
André A
AA
Hirata
Rosario D C
RD
D000368:Aged; D000483:Alleles; D000069059:Atorvastatin; D044383:Black People; D015992:Body Mass Index; D001938:Brazil / Q000453:epidemiology; D008078:Cholesterol, LDL / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D011758:Pyrroles / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008078:Cholesterol, LDL; D017931:DNA Primers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D004247:DNA; D000069059:Atorvastatin; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A