Frequencies of the C1236T, G2677T/A, and C3435T Polymorphisms of the MDR1 Gene and their Haplotypes in Uzbekistan

Abstract

P-glycoprotein (P-gp) is encoded by the MDR1 gene and is involved in the pharmacokinetics of drugs. The best-known MDR1 gene polymorphisms are 1236C>T, 3435C>T, and 2677G>T/A, which are associated with protein folding, changes in mRNA levels, and drug pharmacokinetics. The aim of this study was to identify the frequency of distribution of functional polymorphisms C1236T, C3435T, G2677T/A of the MDR1 gene and their haplotypes in Uzbekistan. For this research, peripheral blood samples were obtained from 218 apparently healthy people from Uzbekistan. MDR1 gene polymorphisms were genotyped by Polymerase Chain Reaction (PCR) and restriction analysis (RFLP). The results of genotyping of the MDR1 gene C1236T variant in 21 volunteers showed that the frequency of the T allele was 58.7%, and the C allele was 41.3% (P = 0.377891). The frequency of the occurrence of the alleles for polymorphism 2677G>T/A was as follows: G, 94.5%; A, 5.5% (P>0.005). For variant 3435C>T, the frequency of the C allele was 43% and the frequency of the T allele was 57% (P = 0.561084). This study also evaluated the simultaneous presence of the C1236T, C3435T, and G2677T/A polymorphisms of the MDR1 gene. The most frequently occurring combination of genotypes was CT/GG/CT (26.1%) and TT/GG/TT (17.4%). The frequency of the common haplotype CGC, representing the simultaneous appearance of all wild-type alleles in the tested MDR1 SNPs, was 6.4% (n = 14) in people with a normal genotype. However, the simultaneous presence of polymorphic nucleotides for all polymorphisms (TAT) was not found. The research made it possible to establish the distribution of allele frequencies of the MDR1 gene of C3435T and C1236T polymorphisms among the samples of our study in Uzbekistan. The frequency occurrence of the CT and TT genotypes for both polymorphisms is higher than that of the CC genotype. Although the obtained results are insufficient to assess the frequency of distribution of polymorphisms in all Uzbekistan residents, further research will be focused on the study of these polymorphisms in a wide range to confirm the reliability of the results.