Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR‐1 in the Egyptian population

Abstract

Genotype and allele frequencies of TPMT , NAT2 , GST , SULT1A1 and MDR-1 in the Egyptian population Aims The goal of this study was to determine the frequencies of important allelic variants in the TPMT , NAT2 , GST, SULT1A1 and MDR-1 genes in the Egyptian population and compare them with the frequencies in other ethnic populations.Methods Genotyping was carried out in a total of 200 unrelated Egyptian subjects. TPMT * 2 was detected using an allele-specific polymerase chain reaction (PCR) assay. TPMT * 3C and NAT2 variants (* 5 , * 6 and * 7 ) were detected using an allelespecific real-time PCR assay. Detection of GSTM1 and GSTT1 null alleles was performed simultaneously using a multiplex PCR assay. Finally, a PCR-restriction fragment length polymorphism assay was applied for the determination of TPMT * 3A (* 3B ) , SULT1A1 * 2 and MDR-1 ( 3435T ) variants.Results Genotyping of TPMT revealed frequencies of 0.003 and 0.013 for TPMT * 3A and TPMT * 3C , respectively. No TPMT * 2 or * 3B was detected in the analysed samples. The frequencies of specific NAT2 alleles were 0.215, 0.497, 0.260 and 0.028 for * 4 (wild-type), * 5 (341C), * 6 (590A) and * 7 (857A), respectively. GSTM1 and GSTT1 null alleles were detected in 55.5% and 29.5% of the subjects, respectively. SULT1A1 * 2 was detected at a frequency of 0.135. Finally, the frequencies of the wild-type allele ( 3435C ) and the 3435T variant in the MDR-1 gene were found to be 0.6 and 0.4, respectively. Conclusions We found that Egyptians resemble other Caucasians with regard to allelic frequencies of the tested variants of NAT2 , GST and MDR-1 . By contrast, this Egyptian population more closely resemble Africans with respect to the TPMT * 3C allele, and shows a distinctly different frequency with regard to the SULT1A1 * 2 variant. The predominance of the slow acetylator genotype in the present study (60.50%) could not confirm a previously reported higher frequency of the slow acetylator phenotype in Egyptians (92.00%), indicating the possibility of the presence of other mutations not detectable as T341C, G590A and G857A. The purpose of our future studies is to investigate for new polymorphisms, which could be relatively unique to the Egyptian population.

Sequence analysis of theN-acetyltransferase 2 gene (NAT2) among Jordanian volunteers

“…The present study compared the NAT2 allele frequencies among Jordanians, found in this study, with the frequencies reported among the major ethnic groups in HapMap data [23], Egyptian [24] and Saudi Arabian [25]. This study found that Chinese Asians had a significant difference (χ 2 , p  < 0.05) in all NAT2 allele frequencies, in comparison with Jordanians (Table 4).…”

Nutritional Countermeasures Targeting Reactive Oxygen Species in Cancer: From Mechanisms to Biomarkers and Clinical Evidence

“…Similarly, differences in GST P activity caused by a genetic polymorphism have been found to correlate with oxidative DNA damage and breast cancer (227). Interestingly, various studies have revealed that genetic variations in several of the antioxidant-related genes are very common throughout the world and may vary among different ethnic and racial communities (1,31,135,188). Since antioxidant supplementation trials did not take into account the single-nucleotide polymorphisms within the genes for the antioxidant enzymes in the corresponding populations, this could be one of the explanations of these trials' contradictory results.…”

Glutathione S Transferases: Biochemistry, Polymorphism and Role in Colorectal Carcinogenesis

“…GSTs exhibit Seindependent glutathione peroxidase activity toward 1-palmitoyl-2-(13-hydroperoxy-cis-9,trans-11-octadecadienoyl)-L-3-phosphatidylcholine and phosphatidylcholine hydroperoxide, reducing lipid hydroperoxides within membranes [18][19][20]. The transferases can also reduce cholesteryl hydroperoxides [21] and fatty acid hydroperoxides, including (S)-9-hydroperoxy-10,12-octadecadieonic acid and (S)-13-hydroperoxy-9,11-octadecadieonic acid [20]. Among the end-products of lipid peroxidation, GSTs conjugate GSH with the 2-alkenals acrolein and crotonaldehyde, as well as 4-hydroxy-2-alkenals of between 6 and 15 carbon atoms in length [22].…”