Genotype Variability and Haplotype Profile of Abcb1 (Mdr1) Gene Polymorphisms in Macedonian Population

Abstract

The aim of this study was to evaluate the most common ABCB1 (MDR1, P-glycoprotein) polymorphisms in the population of R. Macedonia and compare the allele and haplotype frequencies with the global geographic data reported from different ethnic populations. The total of 107 healthy Macedonian individuals from the general population was included. Genotypes for the ABCB1 for three polymorphisms C1236T [rs1128503], G2677A/T [rs2032582] and C3435T [rs1045642] were analyzed by Real-Time PCR. Obtained allele frequencies for these three SNPs were similar to those observed in other European Caucasians. The detected genotype frequencies were 33.6% for 1236CC, 44.9% for 1236CT and 21.5% for 1236TT in exon 12; 32.7%, 44.9% and 22.4% for 2677GG, 2677GT and 2677GT consecutively in exon 21; and 25.2% for 3435CC, 52.3% for 3435CT and 22.5% for 3435TT in exon 26.Strong LD was observed in our study among all = 0.859, r 2 = 0.711). Eight different haplotypes were identified and the most prominent was the CGC haplotype (45.3%). Our study was the first to have documented the distribution of ABCB1 alleles, genotypes and haplotypes in the population of R. Macedonia. The obtained results can help in the prediction of different response to the drugs that are P-glycoprotein substrates. Additionally, in the era of individualized medicine the determination of the P-glycoprotein genotype might be a good predictive marker for determination of the subpopulations with higher risk to certain diseases.

ABCB1 gene polymorphisms is not associated with drug-resistant epilepsy in Romanian children

“…For example, in our study 1236C allele had a frequency of 51.6 % in healthy population, same results being reported in Macedonians (56%), Serbians (53%), Germans and Hungarians (55%) but not in a gipsy (44%) and Slovenians (39%) [32][33][34]. 2677G allele frequency in our study was found in 51% of patients, similar to other European populations (from 53 to 56%).…”

“…[37,38] A strong association for C1236T and G2677T linkage disequilibrium was observed in a Macedonian study. [32] When we analysed the linkage between these two SNPs the most frequent genotype we found was CT/GT, followed by CC/GG and TT/TT, but no statistical differences were detected between the study groups or associated with drug-resistant epilepsy. In a study conducted in Romania, using a group of 70 epileptic children with idiopathic and symptomatic epilepsy, in which three MDR1 polymorphisms (C3435T, G2677T and C129T) were monitored, Buzoianu et al did not succeeded demonstrate association of these polymorphisms to drug resistant epilepsy, even after patients on monoterapy selection.…”

“…[4] A highly significant linkage disequilibrium was shown among exons 12, 21, 26 in MDR1 gene (C1236T, G2677T, C3435T). [17] Naumovska et al [32] concluded in their study that CG haplotype was over-represented in the study population, followed by TT haplotype. In our study, CT/GT haplotypes derived from C1236T and G2677T polymorphisms were associated with response to antiepileptic treatment, with a statistical significance of p-0.03, but we found the same associations as those previously described, in our control group.…”

<b><i>ABCB1</i></b> and <b><i>SLCO1B3</i></b> Gene Polymorphisms and Their Impact on Digoxin Pharmacokinetics in Atrial Fibrillation Patients among the Tunisian Population

“…Our data showed similar allele and genotype distributions of 1236C>T, 2677G>T/A SNPs with the general frequencies reported in European Caucasians [10,28,29] but different from those described in Asian populations including Japanese [30,31], Chinese, and Indian [32,33,34]. The allele and genotype distributions of 3435C>T SNP were compatible to those reported in Asian studies [30,31,32,33,34], while they differed from those described in European [10,28,29], African American, and Sub-Saharan African populations [35]. …”

Association of variants within the GST and other genes with anti-tubercular agents related toxicity: a systematic review and meta-analysis

“…For the analyses of the rs1045642 SNP of the ABCB1 gene, and the rs4149056 and rs4149014 SNPs of the SLCO1B1 gene, substantial heterogeneity was observed; this may be due the variable frequencies of genotypes across different geographical areas. Indeed, allele frequencies have been found to vary considerably between different ethnic populations for the rs1045642 SNP (61), for the rs4149056 SNP (also known as SLCO1B1 521T-C) (62) and the rs4149014 SNP (63).…”