The Founder Effect? -FXIII Deficiency in Southeast Iran: A Molecular Study Report

authors:

avatar Hojat Shahraki ORCID , * , avatar Akbar Dorgalaleh 1 , avatar Majid Fathi 2 , avatar Shadi Tabibian 1 , avatar Shahram Teimourian 3 , avatar Hasan Mollanoori 3 , avatar farhad zaker 1

1 - Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
2 - Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences. Tehran- Iran
3 - Department of Medical Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Journal of Cellular & Molecular Anesthesia: Vol.5, issue 4; e149647
article type: Original Articles
DOI: https://doi.org/10.22037/jcma.v5i4.31852

how to cite: Shahraki H, Dorgalaleh A, Fathi M, Tabibian S, Teimourian S, et al. The Founder Effect? -FXIII Deficiency in Southeast Iran: A Molecular Study Report. J Cell Mol Anesth. 2020;5(4):e149647. https://doi.org/10.22037/jcma.v5i4.31852.

Abstract

Background: Congenital factor XIII (FXIII) deficiency is an extremely rare bleeding disorder (RBD) with different clinical coagulation disorders and great impacts on the perioperative patient outcome. Its prevalence in Southeast Iran is approximately 4,000 times higher than the worldwide prevalence, with Trp187Arg (c.559T> C as the only causative mutation of FXIIID there. We investigated the founder effect of rs1742924, rs4960181, rs3778360 and rs4142290 using haplotype analysis to define the genetic phenomenon in this geographic region. Materials and Methods: In a case-control study, 10 patients with FXIIID and 10 healthy individuals were assessed. Initially, Trp187Arg (c.559T> C) mutation was assessed in all study populations using a PCR-RFLP technique, then haplotype analysis was performed by assessing rs1742924, rs4960181, rs3778360 and rs4142290 polymorphisms. Data were analyzed using a two-proportion z-test. Results: All patients were homozygote for Trp187Arg (c.559T>C), and this mutation was not observed in any form of homozygote or heterozygote in the control group. Polymorphisms in rs1742924, rs4960181, and rs377836 were homozygote (TT, GG, GG, respectively) and T, G, and G alleles distribution in cases and controls with significant difference (P<0.001, P<0.001, and P=0.01 respectively). Rs4142290 polymorphism showed no significant difference between patients and controls (P=0.3). Two types of haplotypes were observed in the case group, and haplotype number 1* was observed among 90% of them, while not observed in the control group. Conclusion: It seems that founder effectors of haplotype number *1 have more antiquity versus other haplotypes, and probably founder effect is responsible for this high prevalence of FXIIID in the southeast of Iran.