Evaluating the relationship between the mitochondrial DNA copy number alterations and amyloidosis risk in familial mediterranean fever patients

Familial Mediterranean Fever (FMF) is an autosomal recessive monogenic autoinflammatory disease that is common in Mediterranean-populated communities. FMF Phenotype type I is characterized by recurrent fever and inflammation of the serous membranes (peritonitis, synovitis or pleuritis) whereas phenotype II is used in a patient without recurrent inflammation and fever with amyloidosis as the first finding. Clinical findings, family history, biochemical tests and genetic laboratory data are used in the diagnosis of FMF. The only therapeutic option to protect against FMF attacks and complications is colchicine molecule. Currently, there is a very large number of patients who are indicated for renal hemodialysis due to chronic renal failure, because of delayed diagnosis of FMF and/or disability of the patient's use of colchicine or resistance to colchicine. There may be a physiopathological basis for the mitochondrial dysfunction with changes in the number of mitochondrial DNA copies in FMF. FMF is a disease with limited biomarkers and amyloidosis that is a frequent and important complication, such as chronic renal failure. For this reason, it is considered that the changes in the number of different mitochondrial DNA copy number variations, detected in different clinical groups will be an important parameter in preventing the diagnosis, follow-up and complications of the disease. In our study, changes in the mitochondrial DNA copy number between 50 patients with FMF, who have M694V homozygote mutation in MEFV gene and amyloidosis and 50 healthy controls, who have not any MEFV mutation or FMF clinical finding, were examined. As a result, a significant decrease in the amount of mitochondrial DNA was detected in FMF patients with M694V homozygous mutation carriers who developed amyloidosis compared to the control group (p<0.001). In this study, mitochondrial dysfunction, which has been identified through changes in the mitochondrial genome in many diseases, has been identified by showing that the copy number variations of mitochondrial DNA in leukocytes also decreases for FMF disease. New research is needed in different study groups to understand the change in severity of mitochondrial dysfunction among different clinical groups within the disease itself.