Maryam Hosseini moghadam - Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Arman moradi - Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Shabnam Boudagh - Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Zahra Ghaemmaghami - Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Majid Maleki - Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Seyed Javad Mowla - Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Introduction: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol (LDL-C) in blood, leading to an increased risk of premature cardiovascular diseases. Gain and loss of function mutations of PCSK9 have been associated to hypercholesterolemia and hypocholesterolemia, respectively. Currently, two FDA approved drugs, Repata and Praluent, inhibitors of PCSK9, administrated in some patients suffering from dyslipidemia.Material and methods: In this study, we investigated probable nucleotide changes in PCSK9 gene of 10 patients who referred to Rajaei Cardiovascular Medical and Research center because of familial hypercholesterolemia. The genomic DNA of all patients was extracted, using salting out method, and PCR amplification and Sanger sequencing was applied by specific designed oligonucleotides. Results: Our data revealed a probable pathogenic nucleotide change in 5’UTR of one patient. Although other patients have nucleotide changes in exons and introns of PCSK9 gene, they are almost belong to benign or likely benign variations. Conclusion: It has been exhibited that some dyslipidemia patients who are resistant to statin drugs have mutation in PCSK9 gene. After evaluating this variant in other family members of the patient, we conclude that nucleotide variation in 5’UTR of the PCSK9 gene may cause hypercholesterolemia in this patient who responses to Repata drug.

PCSK9, hypercholesterolemia, Pathogenic mutation