Examining the Role of Polymorphisms in Exon 25 of the PKD1 Gene in the Pathogenesis of Autosomal Dominant Polycystic Kidney Disease in Iranian Patients

摘要

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent life-threateningmonogenic disorder with high morbidity and mortality. Roughly 1:400-1000 individuals are affected with thisdisease worldwide. The development of ADPKD is largely attributed to mutations in the polycystic kidneydisease (PKD)1 and PKD2 genes. However, the pathogenicity of the different polymorphisms in PDK1 in thedevelopment of ADPKD remains unclear. The aim of this study was to further elucidate the role of thepolymorphisms in exon 25 of the PDK1 gene in relation to the pathogenesis of ADPKD in Iranian patients.Methods: The genomic DNA of 36 Iranian patients with ADPKD was isolated using the standard salting outmethod. The PCR products were directly sequenced and analyzed.Results: The frequencies of CAGGAG, ATGGTG, GTCGTA, and GTGATG polymorphisms in exon 25of the PKD1 gene were 34 (94.44%), 33 (91.67%), 26 (72.22%), and 5 (13.89%), respectively. The most frequentpolymorphism associated with ADPKD was the homozygous CAG→GAG which causes an amino acid changeof Q[Gln] to E[Glu] at codon 3005.Conclusions: Our data suggests that there is potentially a common polymorphism of PDK1 among the Iranianpopulation with ADPKD. This may aid in the diagnosis and genetic screening of at-risk patients for ADPKD.