Genetic Variability and Haplotype Profile of MDR1 (ABCB1) in Roma and Hungarian Population Samples with a Review of the Literature

Abstract

The genetic variability, haplotype profile and ethnic differences of MDR1 polymorphisms in healthy Roma and Hungarian populations were analyzed and the results were compared with those of other populations available from the literature. Healthy subjects (465 Roma and 503 Hungarian) were genotyped for C1236T, G2677T/A and C3435T variants of MDR1 by PCR-RFLP assay. Differences were found between the Roma and Hungarian populations in the frequencies of MDR1 1236 CC (20.7 vs. 33.2%) and TT genotypes (30.8 vs. 21.9%), in T allele frequency (0.551 vs. 0.443) (p < 0.002), and in 3435T allele frequency (0.482 vs. 0.527, p < 0.04). Furthermore, the frequency of CGC, CGT and CTT haplotypes was significantly higher in the Hungarian population than in Roma (41.4 vs. 35.3%, 9.04 vs. 6.02% and 2.88 vs. 1.08%, respectively; p < 0.009), whereas the frequency of TGC and TTC haplotypes was higher in the Roma population than in the Hungarian (7.31 vs. 1.68% and 6.67 vs. 2.08%, respectively; p < 0.001). The prevalence of MDR1 polymorphisms in the Hungarian population is similar to that of other European populations; however, some differences were observed in the haplotype structures. In contrast, the Roma population differs from Hungarians, from Caucasians and from populations from India in the incidence of MDR1 common variants and haplotypes.

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

“…The second most frequent haplotype in ethnical Macedonian population is TTT with frequency of 37.8%. This haplotype is considered as the most frequent haplotype in most other populations, Caucasians 41%, Czech 39.3%, Roma 36%, and Hungarian 37.5% [37,52]. The observed difference is probably observed because genotype TT-TT-TT is reported in 15.9%, of our population.…”

“…When analyzing the three most common SNPs C1236T, G2677T/A and C3435T in Asian population, 10 haplotypes were identified in Chinese, 9 in Indians and 6 in Malays [16]. Twelve different haplotypes were identified in Roma, Brought to you by | MIT Libraries Authenticated Download Date | 5/10/18 10:54 AM and 11 in Hungarian population [37]. The most frequent haplotype in our population was CGC (45.3%).…”

“…The homozigocity of wild type 3435CC genotype is highest among African population and lowest in sought-west Asians [37]. The high frequencies of the C-allele in Africans imply overexpression of P-gp [38] which may influence drug absorption and bioavailability especially in CNS.…”

Contribution of ABCB1 gene polymorphisms to breast cancer cells response to chemotherapy

“…Zestawienie przykładowych, powszechnie stosowanych leków będących modulatorami aktywności glikoproteiny P Częstość występowania tych polimorfizmów zależy od badanej populacji, np. występowanie homozygot dzikich (CC1236) i polimorficznych (TT1236) w populacji węgierskiej szacuje się na odpowiednio CC = 33%, TT = 22%, natomiast wśród Romów rozkład ten jest odmienny i wynosi odpowiednio 21% i 31% [16]. W populacji chińskiej i japońskiej wykazano natomiast, że częstość występowania homozygot dzikich (CC1236) jest na poziomie 15%, a homozygot polimorficznych (TT1236) na poziomie 45% (Chińczycy) i 37% (Japończy-cy) [17,18], podczas gdy w populacji francuskiej odpowiednio 33% i 17,5% [19].…”

Association between ABCB1 (MDR1) Gene 3435 C>T Polymorphism and Colchicine Unresponsiveness of FMF Patients

“…A single nucleotide polymorphism in the exon 26 of the gene C3435T was recently associated to P-gly levels, substrate uptake, differences in MDR1 expression, function, drug response, and disease susceptibility. 4,5 Familial Mediterranean fever (FMF) is a genetic disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. Renal failure is most severe complication and may develop without overt crises.…”