Genetic Analysis of the D-LOOP Region of Mitochondrial Genome in Iranian Patients with Familial Adenomatous Polyposis (FAP)

Background and Aim: Familial adenomatous polyposis (FAP) is an Autosomal dominant inherited disorder and a rare form of colorectal cancer (CRC) that is characterized by the development of hundreds to thousands of adenomas in the rectum and colon. Mostly, cancers develop after the advent of the polyps. It appears in both sexes evenly, and the occurrence of the disease is in the second decade of life. Mitochondrial genome mutations have been reported with a variety of Tumors, but the precise role of these mutations in the pathogenicity and tumor progression is not exactly clear. The aim of this study was to evaluate the D-loop region of nucleotide sequences including HVR loci ۱& ۲ and to investigate the association of D-loop polymorphisms with the risk of FAP in mitochondrial DNA in Iranian patients.Methods: . Genomic DNA was extracted from peripheral blood samples of ۵۶ FAP patients and ۴۰ healthy individuals. In this study, we searched for a region of mtDNA (۶۱۶۱-۱۴۹۱) by PCR and sequencing methods. In addition, a polymorphic evaluation of this region was performed through the human mitochondrial genome database (Mitomap).Results: A total of ۲ new mutations (C۱۶۳۳۵T and C۱۶۳۵۲T) were detected in patients, which was first reported in familial adenomatous polyposis. We also assessed the likely biologic importance of the amino acid substitution with the calculation of the interspecies conservation index (CI). The sequence alignment was performed using the multiple sequence alignment software; MEGA۶ and the Standard Protein Blast (blastp). These Bioinformatics predictions indicate that these mutations may disrupt the process of gene expression. Thus, although FAP accounts for a small percentage of colorectal cancers, its timely diagnosis, and especially the pathogenesis in the affected person's family, can prevent the disease from progressing.Conclusion: The results of this study can be used for genetic counseling and prenatal diagnosis and suggest that mutations in non-coding mitochondrial genes may produce defective proteins in the respiratory chain by affecting gene expression process.

Keywords:

Mitochondrial DNA , D loop , Colon cancer , Familial adenomatous polyposis.