Dorofeyeva A. A.

POINT MUTATIONS GENE TOLL-LIKE RECEPTOR (TLR3 AND TLR4) AND BACTERIAL OVERGROWTH SYNDROME

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About the author:	Dorofeyeva A. A.
Heading	CLINICAL MEDICINE
Type of article	Scentific article
Annotation	Evaluate and analyze violations of intestine microbiome in high school students of Donetsk industrial region, depending on the gene mutations and infections factors сarried. 26 high school students were examined. Hydrogen test with lactulose to assess the state of the intestinal flora was used. Bacterial overgrowth syndrome not only in the large, but also in the small intestine was determined. DNA tests, which included analysis of mutations toll-like receptor 3 - TLR3 (mutation Phe412Leu) and toll-like receptor 4 - TLR4 (mutation Asp299Gly), were conducted. DNA were extracted from leukocytes by using the reagent "DNA express blood". Mutations of receptor TLR3 and TLR4 genes in healthy residents of Donetsk region were detected frequently. TLR3 receptor gene mutation was detected in 17 (65.4%) persons. In 11 (42.3%) cases complete homozygous TLR3 mutation (Leu / Leu) were determined. TLR4 receptor gene mutations were detected in 14 (53.8%) students, but homozygous persons for this mutation were not found. The combination of TLR3 and TLR4 genes mutations in 8 (30.7%) persons were observed and mutation of one of these genes only in 10 (38.4%) student were detected. Persons without gene TLR3 mutation prevailed negative breath test, BOS in majority (80.0%) cases was absent. But BOS was absent in 62.2% in individuals with TLR3 mutation. Bacterial overgrows syndrome was identified in 37.8% cases in persons with combination of TLR3 and TLR4 gene mutations (p <0.05). Bacterial overgrowth syndrome in students with TLR4 gene mutation in 66.7% cases were found, which was significantly different from the group with the absence of this mutation (p <0.05). At the same time, significant differences in BOS frequency in persons with TLR3 and TLR4 genes mutations combinations were not found (p <1.0). Incidents of acute viral respiratory infections (AVRI) in all groups of students with or without TLR3 and TLR4 receptors genes mutations were low up to 2 times in year (80.0% - 75.0%) (p <1.0). But one person with homozygous TLR3 mutation (Leu / Leu) had AVRI more than 5 times a year with a long hectic period (5-6 days). Probably, he has violations of systemic immunity due to genetic abnormalities. Thus, in persons with TLR4 gene receptor mutation local mucus barrier and resistant small intestine mucosa were abnormal, which promotes to development of BOS. The presence of TLR3 gene mutation had little effect on these processes. At the same time, neither heterozygous mutations of TLR3, TLR4 mutations had no effect to incidence and duration of AVRI. But the presence of a homozygous TLR3mutation was associated with frequent and prolonged AVRI disease.
Tags	receptor, gene mutation, bacterial growth, resistance
Bibliography	Ardatskaya M. D. Disbakterioz kishechnika / M. D. Ardatskaya // Materia Medica. –2003. - No 2-3. – S. 2-8. Grigoryev A. V. Zheludochno-kishechnyiy trakt kak sreda obitaniya bakteriy. Razdel 1. Morfologiya zheludochno-kishechnogo bakterialnogo biotopa / A. V. Grigoryev // – Moskva; Kiev, - 2004. – 95 s.   Dubinin A. V. Troficheskiye i regulyatornyie svyazi makroorganizma i mikroflory / A. V. Dubinin, V. N. Babin, P. M. Rayevskiy // Klinicheskaya meditsina. – 1991. - No 7. – S. 24-28. Kryuchko T. O. Genetichniy polimorfizm Toll-podibnogo retseptora 4 u dItey z atopichnoyu bronhialnoyu astmoyu / T. O. Kryuchko [i dr.] // Klinicheskaya immunologiya. Allergologiya. Infektologiya. – 2011. - No 5. – S. 115-120. Tkachenko Ye. I. Disbioz kishechnika: Rukovodstvo po diagnostike i lecheniyu / Ye. I. Tkachenko, A. N. Suvorova // – SPb.: Spetslit, - 2007. – 238 s.   Tolstopyatova M. A. Rol retseptorov rozhdennogo immuniteta v razvitii infektsionnoy patologii u novorozhdennyih detey / M. A. Tolstopyatova, G. A. Buslaeva, I. G. Kozlov // Pediatriya. – 2009. – T. 87, No 1. – S. 115-120. Ferwerda B. Functional Consequences of Toll-like Receptor 4 Polymorphisms / B. Ferwerda, M. B. McCall, K. Verheijen [et al.] // Mol. Med. – 2008. – Vol. 14, № 5-6. – P. 346-352. Moser M. 7 Dendritic cell regulation of TH1/TH2 development / M. Moser, K.M. Murphy // Nat. Immunol. – 2000. – Vol. 1. – P. 199-205. Marsik C. The Toll-Like Receptor 4 Asp299Gly snd Thr399Ile Polymorphism Influence the Late Inflammatory Response in Human Endotoxemia / C. Marsik, B. Jilma, C. Joukhadar [et al.] // Clinical Chemistry. – 2005. – Vol. 51, № 11. – P. 2178-2180. Schwartz D. The Genetics of Innate Immunity / David A. Schwartz // CHEST. – 2002. – Vol. 121. – P. 62-68.
Publication of the article	«World of Medicine and Biology» №4(47) 2 part 2014 year, 035-038 pages, index UDK 616.34