BACKGROUND: Human leukocyte antigen G (HLA-G) belongs to non-classical MHC class I molecules that is involved in the suppression of immune response. As HLA-G plays important role in the maintenance of fetal tolerance, its overexpression has been associated with tumor progression. For the regulation of HLA-G levels, genetic variants within the 5' upstream regulatory region (5'URR) are of crucial importance. Our study aimed to analyze the association between 16 HLA-G 5'URR variants, sHLA-G level and clinical variables in glioma patients. METHODS: We investigated 59 patients with gliomas (mean age 54.70 ± 15.10 years) and 131 healthy controls (mean age 41.45 ± 9.75 years). Patient's blood was obtained on the day of surgical treatment. The HLA-G 5'URR polymorphisms were typed by direct sequencing and the plasma level of sHLA-G assessed by ELISA. RESULTS: Haploblock within HLA-G 5'URR consisting of -762T, -716G, -689G, -666T, -633A, followed by -486C and -201A alleles were significantly more frequent in patients with gliomas than in the controls (p < 0.05). No correlation of HLA-G 5'URR variants with sHLA-G plasma level was found. Analysis of HLA-G 5'URR variants with main clinical variables in patients with grade IV gliomas revealed that haploblock carriers of -762CT, -716TG, -689AG, -666GT, -633GA, -486AC, -477GC, -201GA followed by -369AC carriers tend to have lower age at onset as compared to other genotype carriers (p = 0.04). CONCLUSION: Our results suggest genetic association of HLA-G 5'URR variants with risk of developing gliomas and possible contribution of HLA-G to disease pathology.
Multiple sclerosis (MS) is an inflammatory autoimmune disease occurring in genetically sensitive individuals. As migration of immune cells into the CNS is facilitated by the Very Late Antigen 4 (VLA-4) integrin molecule, the VLA4 gene may be considered as a plausible candidate genetic risk factor for susceptibility to MS. Therefore, the objective of our study was to investigate the association between two genetic polymorphisms located in the VLA4 gene and the risk of multiple sclerosis. One hundred seventeen MS patients and 165 control subjects from Slovakia were genotyped for VLA4 gene SNP polymorphisms at positions 269 (C/A) and 3061 (A/G). The same study cohorts were also genotyped for the rs3135388 polymorphism tagging the HLA-DRB1*15:01 allele, which is a known genetic factor associated with susceptibility to develop MS in many populations. Our findings show for the first time that the rs3135388 polymorphism is a strong risk factor for MS in the Slovak population. Investigation of the VLA4 gene polymorphisms revealed a significantly higher frequency of the 3061AG genotype in MS patients compared to the controls (P ≤ 0.05). We suggest that the 3061AG polymorphic variant is an independent genetic risk factor for MS development in our population as it was significantly associated with this disease. The association was also confirmed after applying multivariate logistic-regression analysis adjusted for gender, age and HLA-DRB1*15:01 positivity as possible influencing factors.
- MeSH
- alely MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci * MeSH
- HLA-DRB1 řetězec genetika MeSH
- integrin alfa4beta1 genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- roztroušená skleróza genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Slovenská republika MeSH
Asthma bronchiale je chronická zápalová choroba dýchacích ciest, ktorá sa klinicky prejavuje záchvatmi dýchavičnosti. Na vzniku astmy sa podiel'aju viaceré faktory, najma environmentálne a dědičné, avšak ich přesný mechanizmus pósobenia sa ešte stále študuje. V súvislosti s patogenézou astmy sa skúmajú aj geny umiestnené v HLA - genetickej oblasti. K takýmto génom sa nedávno zařadil aj gén kódujúci neklasickú molekulu HLA-G. Biologický význam HLA-G spočívá v potláčaní imunitnej odpovede a navodzovaní tolerancie. Na základe vyšetrenia sekvencie nukleotidov sa doteraz identifikovalo 47 róznych HLA-G aliel. Významný polymoďizmus zahřňa přítomnost' 14 nukleotidov na 3' konci genu HLA-G, ktorý ovplyvňuje stabilitu mRN A a pravděpodobné aj celkovú hladinu proteinu. V práci sme sa preto zamerali na analýzu přítomnosti tohto inzertu v gene HLA-G u pacientov s astmou. Celkovo sme vyšetřili 176 pacientov a 73 zdravých jedincov. Metodou PCR sme identifikovali jedincov s HLA-G genotypom „+14/+14" (19,89 % vs. 16,44 %), s genotypom „-14/-14" (29,55 % vs. 32,88 %) a heterozygotných jedincov s genotypom „+14/-14" (50,57 % vs. 50,68 %). V porovnaní s kontrolou, hladina preukaznosti/j nebola statisticky významná pri nijakej vyšetrovanej skupině, napriek tomu najváčší statistický rozdiel medzi skupinou pacientov a kontrolou sme zistili pri porovnávaní výskytu genotypu „+14/+14" (p = 0,5964).
Bronchial asthma is a chronic inflammatory disease of respiratory tract characterised by attacks of breathlessness. Many factors are involved in its development, including environmental and genetic factors; nevertheless the precise mechanisms of their contribution have not been completely elucidated until now. In relation to the pathogenesis of asthma, genes located in the HLA region have been intensively studied for many years, including HLA-G. The main biological function of HLA-G includes the participation in the tolerance induction. Similarly to other HLA genes, HLA-G is polymorphic too. By nucleotide sequence analysis 47 various HLA-G alleles have been identified until now. The most important polymorphism includes the presence of 14 bp sequence located in 3’ UTR region of HLA-G gene. It is proposed that this polymorphism is involved in mRNA stability which subsequently affects the levels of HLA-G molecules. The aim of our work was to analyse presence of 14 bp sequence in HLA-G gene in the group of patients suffering from bronchial asthma. Altogether we have analysed 176 asthma patients and 73 healthy individuals. Using PCR method we found individuals with HLA-G genotype „-14/-14“ (29,55% vs. 32,88%), with HLA-G genotype „+14/+14“ (19,89% vs. 16,44%) and those who are heterozygous „+14/-14“ (50,57% vs. 50,68%). No statistical significance has been observed by comparing any analysed group to healthy controls as revealed by parameter p counting, nevertheless, the most statistical difference were found between the „+14/+14“groups of patients and controls (p = 0,5964).
- Klíčová slova
- PCR-analýza,
- MeSH
- bronchiální astma etiologie genetika imunologie MeSH
- DNA analýza MeSH
- genetická predispozice k nemoci MeSH
- genetické testování MeSH
- genotyp MeSH
- HLA-G antigeny analýza MeSH
- lidé MeSH
- messenger RNA MeSH
- polymorfismus genetický MeSH
- statistika jako téma MeSH
- výběr pacientů MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- abstrakt z konference MeSH
Balb/c mice were immunized with the recombinant fusion protein gD1/313 (FpgD1/313 representing the ectodomain of HSV-1 gD), with the non-pathogenic ANGpath gE-del virus, with the plasmid pcDNA3.1-gD expressing full-length gD1 and with the recombinant immediate early (IE) HSV-1 protein ICP27. Specific antibodies against these antigens (as detected by ELISA) reached high titers with the exception of the DNA vaccine. High-grade protection against challenge with the virulent strain SC16 was found following immunization with the pcDNA3.1-gD plasmid and with the gE-del virus. Medium grade, but satisfactory protection developed after immunization with the FpgD1/313 and minimum grade protection was seen upon immunization with the IE/ICP27 polypeptide. A considerable response of peripheral blood cells (PBL) and splenocytes in the lymphocyte transformation test (LTT) was found in mice immunized with FpgD1/313, with the pcDNA3.1-gD plasmid and with the live ANGpathgE-del virus. For lymphocyte stimulation in vitro, the FpgD1/313 antigen was less effective than the purified gD1/313 polypeptide (cleaved off from the fusion protein); both proteins elicited higher proliferation at the 5 mug per 0.1 mL dose than at the 1 mug per 0.1 mL dose. The secretion of Th type 1 (TNF, IFN-gamma and IL-2) and Th type 2 (IL-4 and IL-6) cytokines was tested in the medium fluid of purified PBL and splenocyte cultures; their absolute values were expressed in relative indexes. The PBL from FpgD1/313 immunized mice showed increased secretion of both T(H)1 (TNF) as well as T(H)2 (IL-4) cytokines (7-10-fold, respectively). Splenocytes from FpgD1/313 immunized mice showed a significant (23-fold) increase in IL-4 production.
- MeSH
- aktivace lymfocytů MeSH
- buněčné linie MeSH
- cytokiny biosyntéza imunologie MeSH
- imunizace MeSH
- krevní buňky imunologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- lidský herpesvirus 1 genetika imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- protilátky virové krev MeSH
- Simplexvirus imunologie MeSH
- T-lymfocyty imunologie MeSH
- vakcína proti viru herpes simplex aplikace a dávkování imunologie MeSH
- virové proteiny genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
