The ABCB1 gene was mapped to chromosome 7q21.12, it encodes a cell membrane protein of 1280 amino acids called P-glycoprotein (P-gp). P-glycoprotein is a member of the superfamily of ATP-binding cassette (ABC) transporters that transport chemicals out of cells. P-glycoprotein is expressed in many tissues, including the blood-brain barrier. It functions as a transporter in the blood-brain barrier, and has a broad physiological role and functions by pumping cytotoxic drugs and xenotoxins out of cells into the intestinal lumen, bile, and urine, and, thus, limiting distribution of such compounds to other organs. Normal physiological expression of P-glycoprotein has been found to prevent uptake of some lipophilic drugs into the brain and other key organs. However, P-glycoprotein is extremely overexpressed in cancer cells resulting in drugs being pumped out of the cells faster than they can enter.
The ABCB1 gene is composed of 27 exons, and spans approximately 210 kb in the genomic DNA. More than 50 polymorphisms have been observed in the coding region of the ABCB1 gene. These polymorphisms may be a strong determinant of interindividual variability in resistance to multiple drugs including anticancer agents and epilepsy drugs. Overexpression of P-glycoprotein has been associated with altered drug absorption, therapy resistant malignancies, and lower concentrations of HIV-1 protease inhibitors. The c.C3435T polymorphism is well-known to be associated with AED resistance in epilepsy. Also variations in this gene have been associated with Inflammatory bowel disease 13 (IBD13).
Ameyaw et al. (2001) performed PCR-RFLP assay for ABCB1/MDR1 c.C3435T SNP for 10 different ethnic groups including Saudi Arabia. Ninety six Saudi volunteers were included in the study. The C allele frequency was 55% among the Saudis and was lower than the African populations accounting for 73% among Sudanese. The high frequency of the C allele among Africans may have important therapeutic and prognostic implications.
Al-Mohizea et al. (2012) studied the frequency of three MDR1 gene polymorphisms in the Saudi Arabian population. The study included 192 healthy unrelated Saudi males that were recruited from different geographical regions of the country for this study. The study focused on the most common MDR1 SNPs, namely, C1236T, G2677T/A and C3435T. Allele and haplotype frequencies were determined. It was found that the frequencies for 1236T, 2677T and 3435T were 43.7%, 40.2% and 42.2% respectively. The three variants were found to be in moderate to strong linkage disequilibrium with each other. In addition, 12 different haplotypes were identified in the study. The frequencies of the haplotypes C-G-C and T-T-T were found to be 48.8% (95% CI, 41.5, 55.8) and 35.5% (95% CI, 28.6, 42.3) respectively. The distribution frequencies of the MDR1 polymorphisms and haplotypes determined in this study differed from other ethnic groups, suggesting the need for further investigation.
In order to better understand the mechanism of anticancer drug resistance in the Arab population of Saudi Arabia, Alsaif et al. (2013) analyzed the occurrence of SNPs in the MDR1 gene in 100 breast cancer patients and compared these to a healthy control group of 100 subjects. A significant correlation was found between the genotype at codon 1236 (exon 12) and the response to chemotherapy regimens. The CT/TT genotype at this position showed a low response to therapy.
[See: Saudi Arabia > Ameyaw et al., 2001].
Ostrovsky et al. (2004) studied 500 individuals belonging to Ashkenazi, Yemenite, North African, Mediterranean, and Near-Eastern Jewish communities. Frequencies of the C allele were quite similar among the Yemenite (0.645), Ashkenazi (0.65), and North-African (0.615) Jewish populations. However, the frequency of this allele was slightly lower among Mediterranean Jews (0.58) and significantly lower among Near-Eastern Jews (0.445).