title: May TLR4 Asp299Gly and IL17 His161Arg polymorphism be associated with progression of primary measles infection to subacute sclerosing panencephalitis?
abstract: SSPE is a progressive neurological disorder of children. Only some of the children who are infected with measles virus develop SSPE, which supports individual variation. TLR-2 and TLR-4 play an important role in innate immunity by recognizing envelope proteins of MV. Another important cytokine that plays an important role in orchestrating innate immune function is IL-17. The purpose of our study is to elucidate whether the TLR2, TLR4, IL17F and IL17A gene polymorphisms are susceptibility genes for the development of SSPE. Using the PCR-RFLP methods, the single nucleotide polymorphisms of TLR2 (Arg753Gln, Arg677Trp, -194 to -174 del), TLR4 (Asp299Gly and Thr399Ile) IL17F (His161Arg, Glu126Gly) and IL17A were studied in 54 patients with SSPE and 81 healthy controls. For Asp299Gly polymorphism of the TLR4 gene we found that there were no control individuals who were homozygous carriers of the Gly/Gly genotype, and the risk for SSPE increased at approximately 4.7 fold for the heterozygous carriers of the Asp/Gly genotype (OR 4.727, 95%-CI 1.192-18.742; P=0.01), when compared to healthy controls. Also our findings demonstrate that homozygosity for the Arg161 variant of the IL17F His161Arg polymorphism is inversely associated with development of SSPE (OR 0.114 95%-CI 0.026-0.494; P<0.001). In conclusion, it is suggested that variation in susceptibility to SSPE disease may be in part due to variations in TLR4 and IL17 function resulting from polymorphisms of TLR4 Asp299Gly and IL17F His161Arg.
authors.affiliation: Bulent Ecevit University Faculty of Medicine, Department of Medical Biology, Zonguldak, Turkey. Electronic address: sevimkarakas@hotmail.com.
authors.forename: Sevim
authors.initials: S
authors.lastname: Karakas-Celik
authors.affiliation: Bulent Ecevit University Faculty of Medicine, Department of Pediatrics, Zonguldak, Turkey.
authors.forename: Ibrahim Etem
authors.initials: IE
authors.lastname: Piskin
authors.affiliation: Bulent Ecevit University Faculty of Medicine, Department of Medical Genetic, Zonguldak, Turkey.
authors.forename: Mehmet Fatih
authors.initials: MF
authors.lastname: Keni
authors.affiliation: Harran University Faculty of Medicine, Department of Pediatric Neurology, Sanliurfa, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Calık
authors.affiliation: BezmialemVakif University, Faculty of Medicine, Department of Pediatric Neurology, Istanbul, Turkey.
authors.forename: Akın
authors.initials: A
authors.lastname: Iscan
authors.affiliation: Bulent Ecevit University Faculty of Medicine, Department of Medical Genetic, Zonguldak, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dursun
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D013344:Subacute Sclerosing Panencephalitis / Q000175:diagnosis / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C508717:IL17A protein, human; C440021:IL17F protein, human; D020381:Interleukin-17; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: IL17; Subacute sclerosing panencephalitis; TLR2; TLR4; Toll like receptors