Hayri Levent YILMAZ, Ali Erdinç YALIN, Rıza Dinçer YILDIZDAŞ, Kıymet AKSOY, Gülsüm UÇAR, Fatma Derya ÖZDURAN, Yaşar SERTDEMİR, Özden Özgür HOROZ, Sinem GÖKAY SARI, Mustafa YILMAZ

MyD 88 Polymorphisms in Children Diagnosed with Sepsis

Background: Myeloid differentiation primary response gene 88 (MyD 88) is an intracellular adapter protein that mediates the early immune response to pathogens. Toll-like receptors (except TLR-3) induce the immune response through a MyD 88-dependent signal pathway. Aims: We aimed to investigate the MyD 88 polymorphisms that play important roles in the immune response in septic children and to evaluate whether or not they were risk factors in the development of sepsis. Study Design: Case-control study. Methods: Sixty-five patients diagnosed with sepsis in the Pediatric Intensive Care Unit during the period from April 2010 to January 2012 were included as the study group. Sixty-five children without sepsis were included as controls. After DNA was obtained from blood samples in the study and control groups, MyD 88 polymorphisms were analyzed. According to the genotype and allele frequencies, the distributions of MyD 88 polymorphisms [Single nucleotide polymorphism (SNP) - 938 C/A (rs4988453), MyD 88 SNP 1944 C/G (rs4988457)] were analyzed in both the study and control groups. Results: The C/C genotype of MyD 88 SNP -938 was significantly more common than the C/A genotype in the patient group (p=0.002). No statistically significant difference in the frequency of the MyD 88 SNP 1944 genotype was found between the study and control groups (p=0.272). Conclusion: Gene polymorphism studies could elucidate our understanding of sepsis in terms of prevalence and the managementof treatment. It was shown in this study that children with the MyD 88 SNP -938 C/C genotype had a greater tendency toward sepsis. However, additional studies should be performed.

PDF

___

Somec R, Amaglio N, Spirer and Rechavi G. Genetic predispo- sition to infectious pathogenes; a review of Iess familiar vari- ants. Pediatr Infect Dis J 2003;22:457-61. [CrossRef]
Emonts M, Hazelzet JA, de Groot R, Hermans PW. Host genetic determinants of Neisseria meningitidis infection. Lancet Infect Dis 2003;3:565-77. [CrossRef]
Hubacek JA, Stüber F, Frohlich D, Book M, Wetegrove S, Ritter M, et al. Gene variants of the bactericidal/permeability increas- ing protein and lipopolysaccharide binding protein in sepsis patients: Gender-specific genetic predisposition to sepsis. Crit Care Med 2001;29:557-61. [CrossRef]
Takeda K, Yamamoto M, Honda K. Assessing the response of cells to TLR stimulation. In: Konat GW, editor. Signaling by Toll-like Receptors. 1st edition. Boca Raton: CRC Press; 2008;1-22.
Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Im- munol 2003;21:335-76. [CrossRef]
Bonnert TP, Garka KE, Parnet P, Sonoda G, Testa JR, Sims JE. The cloning and characterization of human MyD88: a member of an IL-1 receptor related family. FEBS Lett 1997;402:81-4. [CrossRef]
Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, et al. MyD88 is an adaptor protein in the hToll/Il-1 receptor family signaling pathways. Mol Cell 1998;2:253-8. [CrossRef]
von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, et al. Pyogenic bacterial infections in humans with MyD88 defi- ciency. Science 2008;321:691-6. [CrossRef]
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6:2-8. [CrossRef]
Song Z, Yin J, Yao C, Sun Z, Shao M, Zhang Y, et al. Vari- ants in the Toll-interacting protein gene are associated with sus- ceptibility to sepsis in the Chinese Han population. Crit Care 2011;15:R12. [CrossRef]
Picard C, Von Bernuth H ,Ghandil P, Chrabieh M, Levy O, Arkwright PD, et al. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine (Baltimore) 2010;89:403-25. [CrossRef]
Plantinga TS, Johnson MD, Scott WK, Van de Vosse E, Velez Edwards DR, Smith PB, et al. Toll-like receptor 1 polymor- phisms increase susceptibility to candidemia. J Infect Dis 2012;205:934-43. [CrossRef]