بررسی فراوانی پلی مورفیسم ژنتیکی C3435T ژن MDR1 در یک جمعیت سالم استان مازندران

Background and purpose: The human multidrug resistance gene (MDR1) encodes for P-glycoprotein (P-gp) which is a transmembrane transporter protein acts as an efflux pump for a number of xenobiotics. It plays a protective role for cells against DNA damage caused by toxins and drugs. The wobble C3435T polymorphism at exon 26 has been associated with different expression levels and activities of this gene. Differences in allele frequency of the C3435T polymorphism have been demonstrated between distinct ethnic groups. In this study, we examined this polymorphism in a healthy population in Mazandaran province (North of Iran). Material and methods: Genomic DNA was extracted from the peripheral leukocytes of 150 healthy volunteers under the supervision of two physicians in Sari Blood Transfusion Center. All subjects gave their written informed consent to participate in the research. Polymerase chain reaction–restriction fragment length polymorphism method was used for the detection of C3435T single nucleotide polymorphism and the results were confirmed by direct sequencing method. Results: The frequencies of the CC, CT and TT genotypes were 10.7 %, 64 % and 25.3%, respectively. The frequency of T allele (57.3%) was significantly higher than C allele (42.7 %) (P<0.05). Conclusion: This study is the first to show the C3435T polymorphism of MDR1 gene in a population in Mazandaran province of Iran. These data may be relevant for dose recommendation of P-gp substrate drugs and can help for individualizing drug therapy of organ transplantation and important diseases such as cancer and AIDS, congestive heart failure and others.