A Study on Mutation of the Exon 10 of the LDLR gene in Hypercholesterolemia Patients in Ardebil, Iran

Authors
M. Ghadiry
H. Yaghoubi
Department of Biology, Ardabil Branch, Islamic Azad University, Ardabil, Iran
Abstract
Objective: Familial hypercholesterolemia (FH) is an autosomal dominant disease mainly attributed to mutations in the low-density lipoprotein receptor gene (LDLR). This study aims to investigate molecular changes in the LDLR gene in patients with high cholesterol in individuals from Ardebil Province, Iran.
Methods: We evaluated 100 patients with suspected FH from Ardebil Province. DNA samples using primers LDLR gene and exon 10 PCR-SSCP method was tested and modified bands on gel electrophoresis detected and subsequently examined by DNA sequencing.
Results: We evaluated 100 patients with suspected FH, 43 males and 66 females. The average age of 50.68 and 281.81 had average cholesterol levels of the subjects. In this study, we identified a polymorphism 1413G(A LDLR gene. Allele G, 70% of the population studied and the A allele is 30% of the subjects to be included.
Conclusion: The findings of this study showed that polymorphism of the LDLR gene in FH 1413GA was not the main role, but could indirectly affect, and possibly other exons of the gene or other genes in the development of FH in the region have.

Keywords

[1]  De Castro-Oros I, Pocovi M, Civeira F. The genetic basis of familia hypercholesterolemia: inheritance, linkage, and mutation. Appl Cilin Genet 2010; 3: 53-64.
[2]  Fard Esfahani P, Zeinali C, Rouhi Dehboneh S, Taghikhani M, Khatami S. A novel mutation in exon 4 of the Low dencity lipoprotein receptor gene in an Iranian familial hypercholesterolemia patient. IBJ 2005; 9(3): 139-42.
[3]  Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest 2003; 111(12): 1795-803.
[4]  Chater R, Aït Chihab K, Rabès JP, Varret M, Chabraoui L, El Jahiri Y, Adlouni A, Boileau C, Kettani A, El Messal M. Mutational heterogeneity in low-density lipoprotein receptor gene related to familial hypercholesterolemia in Morocco. Clinica Chemica Acta 2006; 373(1-2): 62-9.
[5]  Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986; 232(4746): 34-47.
[6]  Lombardi MP, Redeker EJ, Defesche JC, Kamerling SW, Trip MD, Mannens MM, Havekes LM, Kastelein JJ. Molocular genetic testing for familial hypercholesterolemia: spectrum of LDL receptor gene mutations in the Netherlands. Clin Genet 2000; 57(2): 116-24.
[7]  Whitfield AJ, Barrett PH, van Bockxmeer FM, Burnett JR. Lipid disorders and mutations in the APOB gene. Clin Chem 2004; 50(10): 1725-32.
[8]  Hobbs HH, Brown MS, Goldstein JL. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat 1992; 1(6): 445-66.
[9]  Goldstein JL, Schrott HG, Hazzard WR, Bierman EL, Motulsky AG. Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest 1973; 52(7): 1544-68.
[10] Varret M, Rabes JP, Saint-Jore B, Cenarro A, Marinoni JC, Civeira F, Devillers M, Krempf M, Coulon M, Thiart R, Kotze MJ, Schmidt H, Buzzi JC, Kostner GM, Bertolini S, Pocovi M, Rosa A, Farnier M, Martines M, Junien C, Boileau C. A third major locus for autosomal dominant hypercholesterolemia maps to 1p32. 1-p32. Am J Hum Genet 1999; 64(5): 1378-87.
[11] Hirayama T, Yamaki E, Hata A, Tsuji M, Hashimoto K, Yamamoto M, Emi M. Five familial hypercholesterolemic Kindreds in Japan with novel mutation of the LDL receptor gene. J Hum Genet 1998; 43(4): 250-4.
[12] Chiou KR, Charng MJ. Genetic diagnosis of familial hypercholesterolemia in Han Chinese. J Clin Lipidol 2016; 10(3): 490-6.
[13] Durst R, Ibe UK, Shpitzen S, Schurr D, Eliav O, Futema M, Whittall R, Szalat A, Meiner V, Knobler H, Gavish D, Henkin Y, Ellis A, Rubinstein A, Harats D, Bitzur R, Hershkovitz B, Humphries SE, Leitersdorf E. Molecular genetics of familial hypercholesterolemia in Israel–revisited. Atherosclerosis 2017; 257: 55-63.
[14] Shayesteh F, Farrokhi E, Shirani M, Modarresi M, Roghani F, Hashemzadeh M. The study mutations of the 9 exons of LDLR gene in patients with familial hypercholesterolemia in Cheharmahal Bakhtiari province. AMUJ 2011; 13(4): 30-37. (Persian)
Pathobiology Reserach
Volume 20, Issue 1
June 2017
Pages 43-51