Genetic Analysis of D-Loop Region of Mitochondrial DNA Sequence in Iranian Patients with Familial Adenomatous Polyposis (FAP): A Case-Control Study

Familial adenomatous polyposis (FAP) is an inherited disorder and a rare form of colorectal cancer. This disease appears equally in both sexes and its occurrence is more in the second or third decade of life. Mutations and alterations of the mitochondrial genome, especially the D-loop region, have been reported in various human tumors. But the exact role of these mutations in the pathogenesis and progression of tumors is still unclear. The purpose of the present study was to investigate the occurrence of mtDNA nucleotide mutations in the D-loop region, especially the hypervariable regions (HVR) in FAP patients.

In this case-control study, 56 FAP patients were investigated for mutations in the mitochondrial D-loop region by Touchdown PCR, single-stranded conformation polymorphism (SSCP), and sequencing analysis. Fisher's exact statistical tool was used to find the relationship between these nucleotide changes and the risk of FAP disease.

Nineteen nucleotide changes were identified in the D-loop region of patients with FAP symptoms. Two of these nucleotide changes (C16335T and C16352T) were novel and not previously reported in any disease. The results of the statistical analysis of observed mutations showed a statistically significant difference between the patient's group and the control group (p<0.05).

The findings of this study indicate a positive correlation of mtDNA mutations in the D-loop region in all FAP cases compared to the matched control groups. Therefore, the mutation in mitochondrial non-coding sequences may lead to the production of defective proteins in the respiratory chain by affecting the expression process of mitochondrial genes.