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01-01-2016 | Original Article - Genes and Disease

Association of CD40 polymorphisms and haplotype with risk of systemic lupus erythematosus

Published in: Rheumatology International | Issue 1/2016

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is caused by genetic and environmental factors. Current evidence shows that the CD40–CD40L system plays a crucial role in the development, progression and outcome of SLE. CD40, which stimulates lymphocyte proliferation and differentiation, is an important immunomodulator and is expressed in the thyroid follicular cells as well as antigen-presenting cells. The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to SLE and its impact on CD40 expression in Chinese. We analyzed four single nucleotide polymorphisms of CD40 gene rs1883832C/T, rs13040307C/T, rs752118C/T, and rs3765459G/A in 205 patients with SLE and 220 age- and sex-matched controls, using Snapshot SNP genotyping assays and DNA sequencing method. Soluble CD40 (sCD40) levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of CD40 gene rs1883832 C/T polymorphism between the group of patients with SLE and the control group (P < 0.05). sCD40 levels were increased in patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying the CD40 rs1883832 T variant allele were associated with increased CD40 levels compared with the homozygous wild-type genotype in patients with SLE. The rs1883832 C/T polymorphism of CD40 and its sCD40 levels were associated with SLE in the Chinese population. These data suggest that CD40 gene may play an essential role in the development of SLE.

Asano NM, Angelo HD, da Silva HA, Maia MM, Lins OG, Souza PE (2013) Interleukin-6 promoter polymorphisms-174 G/C in Brazilian patients with systemic lupus erythematosus. Hum Immunol 74:1153–1156PubMedCrossRef

Liu J, Liu J, Ni J, Leng RX, Pan HF, Ye DQ (2015) Association of UBASH3A gene polymorphisms and systemic lupus erythematosus in a Chinese population. Gene 565:116–121PubMedCrossRef

Devaraju P, Gulati R, Antony PT, Mithun CB, Negi VS (2015) Susceptibility to SLE in South Indian Tamils may be influenced by genetic selection pressure on TLR2 and TLR9 genes. Mol Immunol 64:123–126PubMedCrossRef

Barton A, Thomson W, Ke X, Eyre S, Hinks A, Bowes J, Gibbons L, Plant D; Wellcome Trust Case Control Consortium, Wilson AG, Marinou I, Morgan A, Emery P; YEAR consortium, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Worthington J (2008) Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility. Hum Mol Genet 17:2274–2279

Barton A, Worthington J (2009) Genetic susceptibility to rheumatoid arthritis: an emerging picture. Arthritis Rheum 61:1441–1446PubMedCrossRef

Gregersen PK, Olsson LM (2009) Recent advances in the genetics of autoimmune disease. Annu Rev Immunol 27:363–391PubMedPubMedCentralCrossRef

Zhang X, Li S, Zhang Y, Lu Y, Wang J, Xu J, Li X, Qin X (2014) Meta-analysis of the relationship between 14 bp insertion/deletion polymorphism of HLA-G gene and susceptibility to systemic lupus erythematosus. Hum Immunol 75:1171–1176PubMedCrossRef

Chen T, Lin J, Jin S, Ma S, Yu L, Huang K, Huang X, Chu J, Yang Z (2014) Association of three polymorphisms in the 3′ untranslated region of the HLA-G gene with systemic lupus erythematosus in a population from Yunnan. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 31:228–232PubMed

Lucena-Silva N, de Souza VS, Gomes RG, Fantinatti A, Muniz YC, de Albuquerque RS, Monteiro AL, Diniz GT, Coelho MR, Mendes-Junior CT, Castelli Eda C, Donadi EA (2013) HLA-G 3′ untranslated region polymorphisms are associated with systemic lupus erythematosus in 2 Brazilian populations. J Rheumatol 40:1104–1113PubMedCrossRef

10.

Zhang SQ, Han JW, Sun LD, Lu WS, Yin XY, Zhang XJ, Yang S (2011) A single-nucleotide polymorphism of the TNFSF4 gene is associated with systemic lupus erythematosus in Chinese Han population. Rheumatol Int 31:227–231PubMedCrossRef

11.

Zhu Y, Wang J, Feng X (2014) CTLA-4 SNPs (CT60A/G, -1722T/C, -1661G/A, and -318C/T) and systemic lupus erythematosus: a meta-analysis. Crit Rev Eukaryot Gene Expr 24:89–100PubMedCrossRef

12.

Orozco G, Eyre S, Hinks A, Ke X; Wellcome Trust Case Control consortium YEAR Consortium, Wilson AG, Bax DE, Morgan AW, Emery P, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Thomson W, Barton A, Worthington J (2010) Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study. Ann Rheum Dis 69:813–816

13.

Raychaudhuri S, Remmers EF, Lee AT, Hackett R, Guiducci C, Burtt NP, Gianniny L, Korman BD, Padyukov L, Kurreeman FA, Chang M, Catanese JJ, Ding B, Wong S, van der Helm-van Mil AH, Neale BM, Coblyn J, Cui J, Tak PP, Wolbink GJ, Crusius JB, van der Horst-Bruinsma IE, Criswell LA, Amos CI, Seldin MF, Kastner DL, Ardlie KG, Alfredsson L, Costenbader KH, Altshuler D, Huizinga TW, Shadick NA, Weinblatt ME, de Vries N, Worthington J, Seielstad M, Toes RE, Karlson EW, Begovich AB, Klareskog L, Gregersen PK, Daly MJ, Plenge RM (2008) Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet 40:1216–1223

14.

Joo YB, Park BL, Shin HD, Park SY, Kim I, Bae SC (2013) Association of genetic polymorphisms in CD40 with susceptibility to SLE in the Korean population. Rheumatology (Oxford) 52:623–630CrossRef

15.

Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2015) Associations between the functional CD40 rs4810485 G/T polymorphism and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Lupus. doi:10.1177/0961203315583543

16.

Smeets E, Meiler S, Lutgens E (2013) Lymphocytic tumor necrosis factor receptor superfamily co-stimulatory molecules in the pathogenesis of atherosclerosis. Curr Opin Lipidol 24:518–524PubMedCrossRef

17.

Yun Y, Ma C, Ma X (2014) The SNP rs1883832 in CD40 gene and risk of atherosclerosis in Chinese population: a meta-analysis. PLoS ONE 9:e97289PubMedPubMedCentralCrossRef

18.

van Kooten C, Banchereau J (2000) CD40-CD40 ligand. J Leukoc Biol 67:2–17PubMed

19.

Suttles J, Stout RD (2009) Macrophage CD40 signaling: a pivotal regulator of disease protection and pathogenesis. Semin Immunol 21:257–264PubMedCrossRef

20.

Melter M, Reinders ME, Sho M, Pal S, Geehan C, Denton MD, Mukhopadhyay D, Briscoe DM (2000) Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo. Blood 96:3801–3808PubMed

21.

Delmas Y, Viallard JF, Solanilla A, Villeneuve J, Pasquet JM, Belloc F, Dubus I, Déchanet-Merville J, Merville P, Blanco P, Pellegrin JL, Nurden AT, Combe C, Ripoche J (2005) Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40. Kidney Int 68:2068–2078PubMedCrossRef

22.

Park JH, Chang HS, Park CS, Jang AS, Park BL, Rhim TY, Uh ST, Kim YH, Chung IY, Shin HD (2007) Association analysis of CD40 polymorphisms with asthma and the level of serum total IgE. Am J Respir Crit Care Med 175:775–782PubMedCrossRef

23.

Burdon KP, Langefeld CD, Beck SR, Wagenknecht LE, Carr JJ, Rich SS, Freedman BI, Herrington D, Bowden DW (2006) Variants of the CD40 gene but not of the CD40L gene are associated with coronary artery calcification in the Diabetes Heart Study (DHS). Am Heart J 151:706–711PubMedCrossRef

24.

Chen F, Hou S, Jiang Z, Li F, Chen Y, Kijlstra A, Yang P (2011) CD40 polymorphisms in Han Chinese patients with Fuch uveitis syndrome. Mol Vis 17:2469–2472PubMedPubMedCentral

25.

Yan JC, Ma GS, Wu ZG, Kong XT, Zong RQ, Zhan LZ (2005) Increased levels of CD40–CD40 ligand system in patients with essential hypertension. Clin Chim Acta 355:191–196PubMedCrossRef

26.

Li M, Sun H, Liu S, Yu J, Li Q, Liu P, Shen H, Sun D (2012) CD40 C/T-1 polymorphism plays different roles in Graves’ disease and Hashimoto’s thyroiditis: a meta-analysis. Endocr J 59:1041–1050PubMedCrossRef

27.

Zhang B, Wu T, Song C, Chen M, Li H, Guo R (2013) Association of CD40–1C/T polymorphism with cerebral infarction susceptibility and its effect on sCD40L in Chinese population. Int Immunopharmacol 16:461–465PubMedCrossRef

28.

Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989PubMedPubMedCentralCrossRef

29.

Odendahl M, Jacobi A, Hansen A, Feist E, Hiepe F, Burmester GR, Lipsky PE, Radbruch A, Dörner T (2000) Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J Immunol 165:5970–5979PubMedCrossRef

30.

Grammer AC, Slota R, Fischer R, Gur H, Girschick H, Yarboro C, Illei GG, Lipsky PE (2003) Abnormal GC reactions in SLE demonstrated by blockade of CD154–CD40 interactions. J Clin Invest 112:1506–1520PubMedPubMedCentralCrossRef

31.

Katsiari CG, Liossis SN, Souliotis VL, Dimopoulos AM, Manoussakis MN, Sfikakis PP (2002) Aberrant expression of the costimulatory molecule CD40L on monocytes from patients with SLE. Clin Immunol 103:54–62PubMedCrossRef

32.

Bishop GA, Moore CR, Xie P, Stunz LL, Kraus ZJ (2007) TRAF proteins in CD40 signaling. Adv Exp Med Biol 597:131–151PubMedCrossRef

33.

Akiyama T, Shimo Y, Yanai H, Qin J, Ohshima D, Maruyama Y, Asaumi Y, Kitazawa J, Takayanagi H, Penninger JM, Matsumoto M, Nitta T, Takahama Y, Inoue J (2008) The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 29:432–437CrossRef

34.

Duffau P, Seneschal J, Nicco C, Richez C, Lazaro E, Douchet I, Bordes C, Viallard JF, Goulvestre C, Pellegrin JL, Weil B, Moreau JF, Batteux F, Blanco P (2010) Platelet CD154 potentiates interferon-alpha secretion by plasmacytoid dendritic cells in systemic lupus erythematosus. Sci Transl Med 2:47ra63PubMedCrossRef

35.

Koshy M, Berger D, Crow MK (1996) Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes. J Clin Invest 98:826–837PubMedPubMedCentralCrossRef

36.

Boumpas DT, Furie R, Manzi S, Illei GG, Wallace DJ, Balow JE (2003) Vaishnaw A; BG9588 Lupus Nephritis Trial Group. A short course of BG9588(anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum 48:719–727PubMedCrossRef

37.

Vazgiourakis VM, Zervou MI, Choulaki C, Bertsias G, Melissourgaki M, Yilmaz N, Sidiropoulos P, Plant D, Trouw LA, Toes RE, Kardassis D, Yavuz S, Boumpas DT, Goulielmos GN (2011) A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression: implications for the pathogenesis. Ann Rheum Dis 70:2184–2190PubMedCrossRef

38.

Piotrowski P, Lianeri M, Wudarski M, Olesinska M, Jagodzinski PP (2013) Single nucleotide polymorphism of CD40 region and the risk of systemic lupus erythematosus. Lupus 22:233–237PubMedCrossRef

Title: Association of CD40 polymorphisms and haplotype with risk of systemic lupus erythematosus
Publication date: 01-01-2016
Published in: Rheumatology International / Issue 1/2016
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-015-3345-7

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