Genetic Analysis of Iranian Patients with Familial Hypercholesterolemia

Authors
Mahdis Ekrami 1
Maryam Torabi 2
Soudeh Ghafouri-Fard 3
Javad Mowla 1
Bahram Mohammad Soltani 1
Feyzollah Hashemi-Gorji 4
Zahra Mohebbi 1
Mohammad Miryounesi 4
1 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2 Department of Genetics, Faculty of Basic Sciences, Islamic Azad University, Zanjan Branch, Zanjan, Iran
3 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
10.22034/ibj.22.2.117
Abstract
Background: Familial hypercholesterolemia (FH) is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B 100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iranian population. Methods: Eighty unrelated Iranian patients with FH entered the study, based on Simon Broome diagnostic criteria. All samples were screened for two common APOB gene mutations, including R3500Q and R3500W, by the means of ARMS-PCR and PCR- RFLP assays, respectively. In addition, exons 3, 4, 9, and 10 of LDLR gene were sequenced in all patients. Results: A novel mutation in exon 3 (C95W) and a previously described mutation in exon 4 (D139H) of LDLR gene were found. Three previously reported polymorphisms in LDLR gene as well as three novel polymorphisms were detected in the patients. However, in the studied population, no common mutations were observed in APOB gene. Conclusion: The results of our study imply that the genetic basis of FH in Iranian patients is different from other populations.
Keywords
Apolipoprotein B 100
Hypercholesterolemia
Genetics
Low-density lipoprotein receptor