#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Galectin-9 gene (LGALS9) polymorphisms are associated with rheumatoid arthritis in Brazilian patients


Autoři: Kamila de Melo Vilar aff001;  Michelly Cristiny Pereira aff001;  Andrea Tavares Dantas aff001;  Moacyr Jesus Barreto de Melo Rêgo aff001;  Ivan da Rocha Pitta aff003;  Ângela Luzia Branco Pinto Duarte aff002;  Maira Galdino da Rocha Pitta aff001
Působiště autorů: Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco (UFPE), Recife, Pernambuco, Brazil aff001;  Rheumatology Service, Clinical Hospital, UFPE, Recife, Pernambuco, Brazil aff002;  Laboratory for Planning and Synthesis of Drugs (LPSF) of the Federal University of Pernambuco (UFPE), Recife, Pernambuco, Brazil aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223191

Souhrn

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and hyperplasia, as well as cartilage and bone destruction. Several proteins are associated with the pathogenesis of the disease. Galectin-9 belongs to the family of lectins that are involved in various biological processes and have anti-inflammatory activity.

Objective

To investigate associations between the SNPs of the GAL-9 gene (LGALS9) and serum levels in rheumatoid arthritis patients. We extracted DNA from 356 subjects, 156 RA patients and 200 healthy controls from northeastern Brazil. Three polymorphisms (rs4795835, rs3763959, and rs4239242) in the LGALS9 gene were selected and genotyped using TaqMan SNP genotyping assay. Serum concentrations of galectin-9 were analyzed by ELISA.

Results

The rs4239242 TT genotype showed a positive association with RA (p = 0.0032, odds ratio = 0.28), and heterozygous TC were prevalent in the control group compared to RA patients (p = 0.0001, odds ratio = 7.99). Galectin-9 serum levels were significantly increased in RA patients compared to the control group (p<0.0001). Patients in remission had high levels of galectin compared to the moderate activity group (p<0.0001). Regarding the Clinical Disease Activity Index (CDAI), patients in remission or low activity presented high levels of galectin when compared to patients in severity (p<0.0001). Patients performing moderate activity had a significant value compared to patients who were in high disease severity (p = 0.0064). Interestingly, the AG genotype (rs3763959) has been associated with a higher presence of bone erosion in RA patients (p = 0.0436). The SNP rs4239242 TT genotype showed a positive association with RA in comparison to the control group. The AG genotype (rs3763959) has been associated with a higher presence of bone erosion in RA patients.

Klíčová slova:

Fibroblasts – Inflammatory diseases – Macrophages – Molecular genetics – Rheumatoid arthritis – Skeletal joints – T cells – Variant genotypes


Zdroje

1. Doody KM, Bottini N, Firestein GS. Epigenetic alterations in rheumatoid arthritis fibroblast-like synoviocytes. Epigenomics. 2017 Apr;9(4):479–492. doi: 10.2217/epi-2016-0151 28322585

2. Glant TT, Mikecz K, Rauch TA. Epigenetics in the pathogenesis of rheumatoid arthritis. BMC Med. 2014 Feb 26;12:35. doi: 10.1186/1741-7015-12-35 24568138

3. Yap HY, Tee SZ, Wong MM, Chow SK, Peh SC, Teow SY. “Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development.” Cells vol. 7,10 161. 9 Oct. 2018.

4. Dhaouadi T, Chahbi M, Haouami Y, Sfar I, Abdelmoula L, Ben Abdallah T, et al. IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis. PLoS One. 2018 Mar 27;13(3):e0194883.

5. John S, Mishra R. Galectin-9: From cell biology to complex disease dynamics. J Biosci. 2016 Sep;41(3):507–34. doi: 10.1007/s12038-016-9616-y 27581941

6. Dai SY, Nakagawa R, Itoh A, Murakami H, Kashio Y, Abe H, et al. Galectin-9 induces maturation of human monocyte-derived dendritic cells. J Immunol. 2005 Sep 1;175(5):2974–81. doi: 10.4049/jimmunol.175.5.2974 16116184

7. Ocaña-Guzman R, Torre-Bouscoulet L, Sada-Ovalle I. TIM-3 Regulates Distinct Functions in Macrophages. Front Immunol. 2016 Jun 13;7:229. doi: 10.3389/fimmu.2016.00229 27379093

8. Seki M, Oomizu S, Sakata KM, Sakata A, Arikawa T, Watanabe K, et al. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis. Clin Immunol. 2008 Apr;127(1):78–88. doi: 10.1016/j.clim.2008.01.006 18282810

9. Seki M, Sakata KM, Oomizu S, Arikawa T, Sakata A, Ueno M, et al. Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts. Arthritis Rheum. 2007; 56:3968–3976. doi: 10.1002/art.23076 18050192

10. Arnett FC, Edworthy SM, Bioch DA, McShane DJ, Fries JF, Copper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–24. doi: 10.1002/art.1780310302 3358796

11. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995 Jan; 38(1):44–8. doi: 10.1002/art.1780380107 7818570

12. Aletaha D, Nell VP, Stamm T, Uffmann M, Pflugbeil S, Machold K, et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther. 2005; 7(4):R796–806. doi: 10.1186/ar1740 15987481

13. Ferraz MB, Oliveira LM, Araujo PM, Atra E, Tugwell P. Crosscultural reliability of the physical ability dimension of the health assessment questionnaire. J Rheumatol. 1990 Jun; 17(6):813–7. 2388204

14. Rodriguez Santiago, Gaunt Tom R. and Day Ian N. M. Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies. American Journal of Epidemiology Advance Access published on January 6,2009.

15. Pál Z, Antal P, Srivastava SK, Hullám G, Semsei AF, Gál J, et al. Non-synonymous single nucleotide polymorphisms in genes for immunoregulatory galectins: association of galectin-8 (F19Y) occurrence with autoimmune diseases in a Caucasian population. Biochim Biophys Acta. 2012 Oct;1820(10):1512–8. doi: 10.1016/j.bbagen.2012.05.015 22683700

16. Hu CY, Chang SK, Wu CS, Tsai WI, Hsu PN. Galectin-3 gene (LGALS3) +292C allele is a genetic predisposition factor for rheumatoid arthritis in Taiwan. Clin Rheumatol. 2011 Sep;30(9):1227–33. doi: 10.1007/s10067-011-1741-2 21475983

17. Panoulas VF, Douglas KM, Smith JP, Metsios GS, Elisaf MS, Nightingale P, et al. Galectin-2 (LGALS2) 3279C/T polymorphism may be independently associated with diastolic blood pressure in patients with rheumatoid arthritis. Clin Exp Hypertens. 2009 Apr;31(2):93–104. doi: 10.1080/10641960802621267 19330599

18. Panoulas VF, Nikas SN, Smith JP, Douglas KM, Nightingale P, Milionis HJ, et al. Lymphotoxin 252A>G polymorphism is common and associates with myocardial infarction in patients with rheumatoid arthritis. Ann Rheum Dis. 2008 Nov;67(11):1550–6. doi: 10.1136/ard.2007.082594 18230628

19. Rosen HR, Golden-Mason L, Daly AK, Yang I, Day CP. Variants in the LGALS9 Gene Are Associated With Development of Liver Disease in Heavy Consumers of Alcohol. Clin Gastroenterol Hepatol. 2016 May;14(5):762–8.e1. doi: 10.1016/j.cgh.2015.11.005 26598225

20. Moriyama K, Kukita A, Li YJ, Uehara N, Zhang JQ, Takahashi I, et al. Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction. Lab Invest. 2014; 1200–11. doi: 10.1038/labinvest.2014.107 25264706

21. Pearson MJ, Bik MA, Ospelt C, Naylor AJ, Wehmeyer C, Jones SW, et al. Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts. Sci Rep. 2018 Aug 27;8(1):12887. doi: 10.1038/s41598-018-31173-3 30150656

22. Lee J, Park EJ, Noh JW, Hwang JW, Bae EK, et al. Underexpression of TIM-3 and blunted galectin-9-induced apoptosis of CD4+ T cells in rheumatoid arthritis. Inflammation. 2012; 35:633–637. doi: 10.1007/s10753-011-9355-z 21717191

23. O'Brien MJ, Shu Q, Stinson WA, Tsou PS, Ruth JH, Isozaki T, et al. A unique role for galectin-9 in angiogenesis and inflammatory arthritis. Arthritis Res Ther. 2018 Feb 12;20(1):31. doi: 10.1186/s13075-018-1519-x 29433546

24. Bradfield PF, Amft N, Vernon-Wilson E, Exley AE, Parsonage G, Rainger GE, et al. Rheumatoid fibroblast-like synoviocytes overexpress the chemokine stromal cell-derived factor 1 (CXCL12),which supports distinct patterns and rates of CD4+ and CD8+ T cell migration within synovial tissue. Arthritis Rheum. 2003 Sep;48(9):2472–82. doi: 10.1002/art.11219 13130466

25. Yeo L, Toellner KM, Salmon M, Filer A, Buckley CD, Raza K, et al. Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann Rheum Dis. 2011 Nov;70(11):2022–8. doi: 10.1136/ard.2011.153312 21742639

26. Arikawa T, Watanabe K, Seki M, Matsukawa A, Oomizu S, Sakata KM, et al. Galectin-9 ameliorates immune complex-induced arthritis by regulating Fc gamma R expression on macrophages. Clin Immunol. 2009; 133:382–392. doi: 10.1016/j.clim.2009.09.004 19800850


Článek vyšel v časopise

PLOS One


2019 Číslo 10
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#