Genotype variability and haplotype frequency of MDR1 (ABCB1) gene polymorphism in Morocco.
The multidrug resistance gene (MDR1) plays an important role in the transport of a wide range of drugs and elimination of xenobiotics from the body. Identification of polymorphisms and haplotypes in the MDR1 gene might not only help understand pharmacokinetics and pharmacodynamics of drugs, but also can help in the prediction of drug responses, toxicity, and side effects, especially, in the era of personalized medicine. We have analyzed the genotypic and haplotypic frequencies of the three most common single-nucleotide polymorphisms in the MDR1 gene in a sample of 100 unrelated healthy Moroccan subjects by polymerase chain reaction-restrictive fragment length polymorphism. The observed genotype frequencies were 43% for 1236CC, 49% for 1236CT, and 8% for 1236TT in exon 12; 49% for 2677GG, 47% for 2677GT, and 4% for 2677TT in exon 21; 39% for 3435CC, 51% 3435CT for 3435TT, and 10% for 3435TT in exon 26, respectively. We found that all polymorphisms were in Hardy-Weinberg equilibrium. Moderate linkage disequilibrium (LD) was observed between the three polymorphisms, the strongest LD in our study has been observed between C1236T and G2677T (D'=0.76; r(2)=0.45). We identified eight haplotypes, the most frequent were 1236C-2677G-3435C (53%), 1236T-2677T-3435T (21%), and 1236C-2677G-3435T (10%), respectively. Our findings might facilitate future studies on pharmacokinetics of P-glycoprotein substrate drugs and interindividual variability to drugs in Moroccan patients.
1 Genetics and Molecular Pathology Laboratory, Medical School of Casablanca, University Hassan II , Casablanca, Morocco .
Yaya
Y
Kassogue
Hind
H
Dehbi
Sanaa
S
Nassereddine
Meryem
M
Quachouh
Sellama
S
Nadifi
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009018:Morocco; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1