Skip to main content
Erschienen in: Acta Neurologica Belgica 3/2020

20.08.2018 | Original Article

High-resolution melting curve analysis of polymorphisms within CD58, CD226, HLA-G genes and association with multiple sclerosis susceptibility in a subset of Iranian population: a case–control study

verfasst von: Reza Ghavimi, Fereshteh Alsahebfosoul, Rasoul Salehi, Mohammad Kazemi, Masoud Etemadifar, Ahmad Zavaran Hosseini

Erschienen in: Acta Neurologica Belgica | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with unknown etiology, which typically is manifested in early to middle adulthood. Recently, genome-wide association studies have identified susceptibility of immune-related genes to be involved in MS predisposition. The goal of the current study was to investigate the association of single nucleotide polymorphisms (SNP) with the immunologically related genes responsible for the disease, composed of CD58 (rs2300747 A>G), CD226 (rs763361 C>T), and HLA-G (rs1611715 A>C), with MS susceptibility. In this case–control study, a total of 200 patients suffering from relapsing-remitting multiple sclerosis and 200 healthy individuals were recruited. DNA was extracted from blood and then all subjects were genotyped for the polymorphism within mentioned genes by high-resolution melting (HRM) real-time PCR method. Statistical analyses were performed using SPSS software (version 20; SPSS, Chicago, IL, USA). Our finding showed that there are significant differences in genotype and allele frequencies between two groups regarding rs763361 (P = 0.035, OR 0.64, CI 95% for C allele) and rs1611715 (P = 0.038, OR 1.57, CI 95% for AA genotype) polymorphisms within CD226 and HLA-G genes, respectively. Concerning rs2300747 polymorphism on CD58 gene, no significant differences were found between cases and controls. In general, results from the current study indicate that CD226 and HLA-G, but not CD58 genetic polymorphisms are associated with increased risk of MS in Isfahan population similar to European populations. However, to elucidate how these SNPs contribute to MS pathogenesis, functional studies are needed.
Literatur
1.
Zurück zum Zitat Weiner HL (2004) Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch Neurol 61(10):1613–1615PubMedCrossRef Weiner HL (2004) Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch Neurol 61(10):1613–1615PubMedCrossRef
2.
Zurück zum Zitat Ku CS, Loy EY, Pawitan Y, Chia KS (2010) The pursuit of genome-wide association studies: where are we now. J Hum Genet 55(4):195–206PubMedCrossRef Ku CS, Loy EY, Pawitan Y, Chia KS (2010) The pursuit of genome-wide association studies: where are we now. J Hum Genet 55(4):195–206PubMedCrossRef
3.
Zurück zum Zitat Nischwitz S, Müller-Myhsok B, Weber F (2011) Risk conferring genes in multiple sclerosis. FEBS Lett 585(23):3789–3797PubMedCrossRef Nischwitz S, Müller-Myhsok B, Weber F (2011) Risk conferring genes in multiple sclerosis. FEBS Lett 585(23):3789–3797PubMedCrossRef
4.
Zurück zum Zitat Schmidt H, Williamson D, Ashley-Koch A (2007) HLA-DR15 haplotype and multiple sclerosis: a HuGE review. Am J Epidemiol 165(10):1097–1109PubMedCrossRef Schmidt H, Williamson D, Ashley-Koch A (2007) HLA-DR15 haplotype and multiple sclerosis: a HuGE review. Am J Epidemiol 165(10):1097–1109PubMedCrossRef
5.
Zurück zum Zitat Hoppenbrouwers IA, Hintzen RQ (2011) Genetics of multiple sclerosis. Biochim Biophys Acta Mol Basis Dis 1812(2):194–201CrossRef Hoppenbrouwers IA, Hintzen RQ (2011) Genetics of multiple sclerosis. Biochim Biophys Acta Mol Basis Dis 1812(2):194–201CrossRef
6.
Zurück zum Zitat Lin X, Deng F-Y, Lu X, Lei S-F (2015) Susceptibility genes for multiple sclerosis identified in a gene-based genome-wide association study. J Clin Neurol 11(4):311–318PubMedPubMedCentralCrossRef Lin X, Deng F-Y, Lu X, Lei S-F (2015) Susceptibility genes for multiple sclerosis identified in a gene-based genome-wide association study. J Clin Neurol 11(4):311–318PubMedPubMedCentralCrossRef
7.
Zurück zum Zitat Bahreini SA, Jabalameli MR, Saadatnia M, Zahednasab H (2010) The role of non-HLA single nucleotide polymorphisms in multiple sclerosis susceptibility. J Neuroimmunol 229(1):5–15PubMedCrossRef Bahreini SA, Jabalameli MR, Saadatnia M, Zahednasab H (2010) The role of non-HLA single nucleotide polymorphisms in multiple sclerosis susceptibility. J Neuroimmunol 229(1):5–15PubMedCrossRef
8.
Zurück zum Zitat Wang JH, Pappas D, De Jager PL, Pelletier D, de Bakker PI, Kappos L et al (2011) Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data. Genome Med 3(1):1CrossRef Wang JH, Pappas D, De Jager PL, Pelletier D, de Bakker PI, Kappos L et al (2011) Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data. Genome Med 3(1):1CrossRef
9.
Zurück zum Zitat Booth DR, Heard RN, Stewart GJ, Goris A, Dobosi R, Dubois B et al (2009) The expanding genetic overlap between multiple sclerosis and type I diabetes. Genes Immunity 10(1):11–14CrossRef Booth DR, Heard RN, Stewart GJ, Goris A, Dobosi R, Dubois B et al (2009) The expanding genetic overlap between multiple sclerosis and type I diabetes. Genes Immunity 10(1):11–14CrossRef
10.
Zurück zum Zitat Patsopoulos NA, de Bakker PI (2011) Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Ann Neurol 70(6):897–912PubMedPubMedCentralCrossRef Patsopoulos NA, de Bakker PI (2011) Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Ann Neurol 70(6):897–912PubMedPubMedCentralCrossRef
11.
Zurück zum Zitat Deckert M, Kubar J, Bernard A (1992) CD58 and CD59 molecules exhibit potentializing effects in T cell adhesion and activation. J Immunol 148(3):672–677PubMed Deckert M, Kubar J, Bernard A (1992) CD58 and CD59 molecules exhibit potentializing effects in T cell adhesion and activation. J Immunol 148(3):672–677PubMed
12.
Zurück zum Zitat Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N et al (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315(5813):848–853PubMedPubMedCentralCrossRef Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N et al (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315(5813):848–853PubMedPubMedCentralCrossRef
13.
Zurück zum Zitat De Jager PL, Baecher-Allan C, Maier LM, Arthur AT, Ottoboni L, Barcellos L et al (2009) The role of the CD58 locus in multiple sclerosis. Proc Natl Acad Sci 106(13):5264–5269PubMedCrossRef De Jager PL, Baecher-Allan C, Maier LM, Arthur AT, Ottoboni L, Barcellos L et al (2009) The role of the CD58 locus in multiple sclerosis. Proc Natl Acad Sci 106(13):5264–5269PubMedCrossRef
14.
Zurück zum Zitat Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+ CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199(7):971–979PubMedPubMedCentralCrossRef Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+ CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199(7):971–979PubMedPubMedCentralCrossRef
15.
Zurück zum Zitat Davis SJ, van der Merwe PA (1996) The structure and ligand interactions of CD2: implications for T-cell function. Immunol Today 17(4):177–187PubMedCrossRef Davis SJ, van der Merwe PA (1996) The structure and ligand interactions of CD2: implications for T-cell function. Immunol Today 17(4):177–187PubMedCrossRef
16.
Zurück zum Zitat Dieude P, Guedj M, Truchetet M-E, Wipff J, Revillod L, Riemekasten G et al (2011) Association of the CD226 Ser307 variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis. Arthrit Rheum 63(4):1097–1105CrossRef Dieude P, Guedj M, Truchetet M-E, Wipff J, Revillod L, Riemekasten G et al (2011) Association of the CD226 Ser307 variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis. Arthrit Rheum 63(4):1097–1105CrossRef
17.
Zurück zum Zitat Du Y, Shen L-X, Yu L-K, Song Y, Zhu J-F, Du R (2012) The CD226 gene in susceptibility of rheumatoid arthritis in the Chinese Han population. Rheumatol Int 32(5):1299–1304PubMedCrossRef Du Y, Shen L-X, Yu L-K, Song Y, Zhu J-F, Du R (2012) The CD226 gene in susceptibility of rheumatoid arthritis in the Chinese Han population. Rheumatol Int 32(5):1299–1304PubMedCrossRef
18.
Zurück zum Zitat Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T et al (1996) DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity 4(6):573–581PubMedCrossRef Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T et al (1996) DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity 4(6):573–581PubMedCrossRef
19.
Zurück zum Zitat Zhang X, Miao J, Zhao F, Yang K, Yang A, Chen L et al. Expression of CD226 antagonizes apoptotic cell death in murine thymocytes. J Immunol. 2009;182(1 Supplement):84.4-84.4 Zhang X, Miao J, Zhao F, Yang K, Yang A, Chen L et al. Expression of CD226 antagonizes apoptotic cell death in murine thymocytes. J Immunol. 2009;182(1 Supplement):84.4-84.4
20.
Zurück zum Zitat Shibuya K, Shirakawa J, Kameyama T, Honda S-i, Tahara-Hanaoka S, Miyamoto A et al (2003) CD226 (DNAM-1) is involved in lymphocyte function—associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation. J Exp Med 198(12):1829–1839PubMedPubMedCentralCrossRef Shibuya K, Shirakawa J, Kameyama T, Honda S-i, Tahara-Hanaoka S, Miyamoto A et al (2003) CD226 (DNAM-1) is involved in lymphocyte function—associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation. J Exp Med 198(12):1829–1839PubMedPubMedCentralCrossRef
21.
Zurück zum Zitat Maiti AK, Kim-Howard X, Viswanathan P, Guillén L, Qian X, Rojas-Villarraga A et al (2010) Non-synonymous variant (Gly307Ser) in CD226 is associated with susceptibility to multiple autoimmune diseases. Rheumatology 49(7):1239–1244PubMedCrossRef Maiti AK, Kim-Howard X, Viswanathan P, Guillén L, Qian X, Rojas-Villarraga A et al (2010) Non-synonymous variant (Gly307Ser) in CD226 is associated with susceptibility to multiple autoimmune diseases. Rheumatology 49(7):1239–1244PubMedCrossRef
22.
Zurück zum Zitat Hafler JP, Maier LM, Cooper JD, Plagnol V, Hinks A, Simmonds MJ et al (2009) CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immunity 10(1):5–10PubMedCrossRef Hafler JP, Maier LM, Cooper JD, Plagnol V, Hinks A, Simmonds MJ et al (2009) CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immunity 10(1):5–10PubMedCrossRef
23.
Zurück zum Zitat Xu Z, Jin B (2010) A novel interface consisting of homologous immunoglobulin superfamily members with multiple functions. Cell Mol Immunol 7(1):11–19PubMedPubMedCentralCrossRef Xu Z, Jin B (2010) A novel interface consisting of homologous immunoglobulin superfamily members with multiple functions. Cell Mol Immunol 7(1):11–19PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Wang JH, Pappas D, De Jager PL, Pelletier D, de Bakker PI, Kappos L et al (2011) Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data. Genome Med 3(1):3PubMedPubMedCentralCrossRef Wang JH, Pappas D, De Jager PL, Pelletier D, de Bakker PI, Kappos L et al (2011) Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data. Genome Med 3(1):3PubMedPubMedCentralCrossRef
25.
Zurück zum Zitat Amodio G, Sales de Albuquerque R, Gregori S (2014) New insights into HLA-G mediated tolerance. Tissue antigens 84(3):255–263PubMedCrossRef Amodio G, Sales de Albuquerque R, Gregori S (2014) New insights into HLA-G mediated tolerance. Tissue antigens 84(3):255–263PubMedCrossRef
26.
Zurück zum Zitat González Á, Rebmann V, LeMaoult J, Horn PA, Carosella ED, Alegre E (2012) The immunosuppressive molecule HLA-G and its clinical implications. Crit Rev Clin Lab Sci 49(3):63–84PubMedCrossRef González Á, Rebmann V, LeMaoult J, Horn PA, Carosella ED, Alegre E (2012) The immunosuppressive molecule HLA-G and its clinical implications. Crit Rev Clin Lab Sci 49(3):63–84PubMedCrossRef
27.
Zurück zum Zitat Curigliano G, Criscitiello C, Gelao L, Goldhirsch A (2013) Molecular pathways: human leukocyte antigen G (HLA-G). Clin Cancer Res 19(20):5564–5571PubMedCrossRef Curigliano G, Criscitiello C, Gelao L, Goldhirsch A (2013) Molecular pathways: human leukocyte antigen G (HLA-G). Clin Cancer Res 19(20):5564–5571PubMedCrossRef
28.
Zurück zum Zitat Pankratz S, Ruck T, Meuth SG, Wiendl H (2016) CD4+ HLA-G+ regulatory T cells: molecular signature and pathophysiological relevance. Hum Immunol 77(9):727–733PubMedCrossRef Pankratz S, Ruck T, Meuth SG, Wiendl H (2016) CD4+ HLA-G+ regulatory T cells: molecular signature and pathophysiological relevance. Hum Immunol 77(9):727–733PubMedCrossRef
29.
Zurück zum Zitat Kenealy SJ, Pericak-Vance MA, Haines JL (2003) The genetic epidemiology of multiple sclerosis. J Neuroimmunol 143(1):7–12PubMedCrossRef Kenealy SJ, Pericak-Vance MA, Haines JL (2003) The genetic epidemiology of multiple sclerosis. J Neuroimmunol 143(1):7–12PubMedCrossRef
30.
Zurück zum Zitat Allan SE, Passerini L, Bacchetta R, Crellin N, Dai M, Orban PC et al (2005) The role of 2 FOXP3 isoforms in the generation of human CD4 + Tregs. J Clin Investig 115(11):3276–3284PubMedCrossRef Allan SE, Passerini L, Bacchetta R, Crellin N, Dai M, Orban PC et al (2005) The role of 2 FOXP3 isoforms in the generation of human CD4 + Tregs. J Clin Investig 115(11):3276–3284PubMedCrossRef
31.
Zurück zum Zitat Liu J, Liu X, Liu Y, Deng S, Huang H, Chen Q et al (2016) Association of EVI5 rs11808092, CD58 rs2300747, and CIITA rs3087456 polymorphisms with multiple sclerosis risk: a meta-analysis. Meta Gene 9:97–103PubMedPubMedCentralCrossRef Liu J, Liu X, Liu Y, Deng S, Huang H, Chen Q et al (2016) Association of EVI5 rs11808092, CD58 rs2300747, and CIITA rs3087456 polymorphisms with multiple sclerosis risk: a meta-analysis. Meta Gene 9:97–103PubMedPubMedCentralCrossRef
32.
Zurück zum Zitat Pandit L, Ban M, Sawcer S, Singhal B, Nair S, Radhakrishnan K et al (2011) Evaluation of the established non-MHC multiple sclerosis loci in an Indian population. Multiple Scler J 17(2):139–143CrossRef Pandit L, Ban M, Sawcer S, Singhal B, Nair S, Radhakrishnan K et al (2011) Evaluation of the established non-MHC multiple sclerosis loci in an Indian population. Multiple Scler J 17(2):139–143CrossRef
33.
Zurück zum Zitat Dardalhon V, Schubart AS, Reddy J, Meyers JH, Monney L, Sabatos CA et al (2005) CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions. J Immunol 175(3):1558–1565PubMedCrossRef Dardalhon V, Schubart AS, Reddy J, Meyers JH, Monney L, Sabatos CA et al (2005) CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions. J Immunol 175(3):1558–1565PubMedCrossRef
34.
Zurück zum Zitat Qiu Z-X, Zhang K, Qiu X-S, Zhou M, Li W-M (2013) CD226 Gly307Ser association with multiple autoimmune diseases: a meta-analysis. Hum Immunol 74(2):249–255PubMedCrossRef Qiu Z-X, Zhang K, Qiu X-S, Zhou M, Li W-M (2013) CD226 Gly307Ser association with multiple autoimmune diseases: a meta-analysis. Hum Immunol 74(2):249–255PubMedCrossRef
35.
Zurück zum Zitat Kim JY, Kim HJ, Cheong HS, Bae JS, Kim J-H, Park BL et al (2012) Lack of association between CD226 genetic variants and inflammatory demyelinating diseases in Korean population. Neuroendocrinol Lett 34(5):402–408 Kim JY, Kim HJ, Cheong HS, Bae JS, Kim J-H, Park BL et al (2012) Lack of association between CD226 genetic variants and inflammatory demyelinating diseases in Korean population. Neuroendocrinol Lett 34(5):402–408
36.
Zurück zum Zitat Liu R, Xu N, Wang X, Shen L, Zhao G, Zhang H et al (2012) Influence of MIF, CD40, and CD226 polymorphisms on risk of rheumatoid arthritis. Mol Biol Rep 39(6):6915–6922PubMedCrossRef Liu R, Xu N, Wang X, Shen L, Zhao G, Zhang H et al (2012) Influence of MIF, CD40, and CD226 polymorphisms on risk of rheumatoid arthritis. Mol Biol Rep 39(6):6915–6922PubMedCrossRef
37.
Zurück zum Zitat Kroner A, Grimm A, Johannssen K, Mäurer M, Wiendl H (2007) The genetic influence of the nonclassical MHC molecule HLA-G on multiple sclerosis. Hum Immunol 68(5):422–425PubMedCrossRef Kroner A, Grimm A, Johannssen K, Mäurer M, Wiendl H (2007) The genetic influence of the nonclassical MHC molecule HLA-G on multiple sclerosis. Hum Immunol 68(5):422–425PubMedCrossRef
38.
Zurück zum Zitat Rizzo R, Bortolotti D, Fredj NB, Rotola A, Cura F, Castellazzi M et al (2012) Role of HLA-G 14 bp deletion/insertion and + 3142C>G polymorphisms in the production of sHLA-G molecules in relapsing-remitting multiple sclerosis. Hum Immunol 73(11):1140–1146PubMedCrossRef Rizzo R, Bortolotti D, Fredj NB, Rotola A, Cura F, Castellazzi M et al (2012) Role of HLA-G 14 bp deletion/insertion and + 3142C>G polymorphisms in the production of sHLA-G molecules in relapsing-remitting multiple sclerosis. Hum Immunol 73(11):1140–1146PubMedCrossRef
39.
Zurück zum Zitat Wiśniewski A, Bilińska M, Klimczak A, Wagner M, Majorczyk E, Nowak I et al (2010) Association of the HLA-G gene polymorphism with multiple sclerosis in a Polish population. Int J Immunogenet 37(4):307–311PubMedCrossRef Wiśniewski A, Bilińska M, Klimczak A, Wagner M, Majorczyk E, Nowak I et al (2010) Association of the HLA-G gene polymorphism with multiple sclerosis in a Polish population. Int J Immunogenet 37(4):307–311PubMedCrossRef
Metadaten
Titel
High-resolution melting curve analysis of polymorphisms within CD58, CD226, HLA-G genes and association with multiple sclerosis susceptibility in a subset of Iranian population: a case–control study
verfasst von
Reza Ghavimi
Fereshteh Alsahebfosoul
Rasoul Salehi
Mohammad Kazemi
Masoud Etemadifar
Ahmad Zavaran Hosseini
Publikationsdatum
20.08.2018
Verlag
Springer International Publishing
Erschienen in
Acta Neurologica Belgica / Ausgabe 3/2020
Print ISSN: 0300-9009
Elektronische ISSN: 2240-2993
DOI
https://doi.org/10.1007/s13760-018-0992-y

Weitere Artikel der Ausgabe 3/2020

Acta Neurologica Belgica 3/2020 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Stuhltransfusion könnte Fortschreiten von Parkinson-Symptomen bremsen

03.05.2024 Parkinson-Krankheit Nachrichten

Kann eine frühzeitige Stuhltransplantation das Fortschreiten von Parkinson-Symptomen verlangsamen? Die Ergebnisse einer randomisierten Phase-2-Studie scheinen dafür zu sprechen.

Frühe Tranexamsäure-Therapie nützt wenig bei Hirnblutungen

02.05.2024 Hirnblutung Nachrichten

Erhalten Personen mit einer spontanen Hirnblutung innerhalb von zwei Stunden nach Symptombeginn eine Tranexamsäure-Therapie, kann dies weder die Hämatomexpansion eindämmen noch die Mortalität senken.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders scheint das auf weibliche Kranke zuzutreffen, wie eine Studie zeigt.

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.