Abstract
Mannose-binding lectin (MBL) serum levels or genetic polymorphisms are known to be associated with autoimmune diseases. We investigated MBL2 genetic polymorphisms in 95 patients with ankylosing spondylitis (AS) and in 252 healthy controls. MBL2 promoter polymorphisms at −550 (H/L), −221 (Y/X), +4 (P/Q), and exon polymorphisms at codon 52 (Arg/Cys), 54 (Gly/Asp, or A/B), and 57 (Gly/Glu) were investigated using polymerase chain reaction and restriction fragment length polymorphism. Genetic polymorphisms were analyzed using SPSS (ver 12.0) and Haploview (ver 4.2). MBL2 single-nucleotide polymorphisms (SNPs) were not significantly different between patients with AS and controls. By haplotype analysis, LYPB frequency was significantly lower in AS (10.7% vs. 21.3%, OR 0.441, 95% CI: 0.266–0.733, P value = 0.001, Pc value = 0.008). The frequency of LYPA (15.4% vs. 9.2%, OR 1.802, 95% CI: 1.097–2.961, P value = 0.019, Pc value = 0.101) and HYPB (3.5% vs. 0.8%, OR 4.457, 95% CI: 1.289–15.409, P value = 0.011, Pc value = 0.060) tended to be higher in AS. Clinical characteristics of AS were not associated with any MBL2 SNP or haplotype. In summary, haplotypes of MBL2 genetic polymorphisms were found to be associated with AS, which suggests that MBL2 genetic polymorphisms may play a role during the development of AS.
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References
FitzGerald O, McInnes I (2006) Spondyloarthropathy: disease at the crossroads of immunity. Best Pract Res Clin Rheumatol 20:949–967
Turner MW (2003) The role of mannose-binding lectin in health and disease. Mol Immunol 40:423–429
Madsen HO, Garred P, Thiel S, Kurtzhals JA, Lamm LU, Ryder LP, Svejgaard A (1995) Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 155:3013–3020
Garred P, Larsen F, Madsen HO, Koch C (2003) Mannose-binding lectin deficiency-revisited. Mol Immunol 40:73–84
Schmiegelow K, Garred P, Lausen B, Andreassen B, Petersen BL, Madsen HO (2002) Increased frequency of mannose-binding lectin insufficiency among children with acute lymphoblastic leukemia. Blood 100:3757–3760
Davies EJ, Snowden N, Hillarby MC, Carthy D, Grennan DM, Thomson W, Ollier WE (1995) Mannose-binding protein gene polymorphism in systemic lupus erythematosus. Arthritis Rheum 38:110–114
Lee YH, Witte T, Momot T, Schmidt RE, Kaufman KM, Harley JB, Sestak AL (2005) The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a meta-analysis. Arthritis Rheum 52:3966–3974
Graudal NA, Homann C, Madsen HO, Svejgaard A, Jurik AG, Graudal HK, Garred P (1998) Mannan binding lectin in rheumatoid arthritis. A longitudinal study. J Rheumatol 25:629–635
Graudal NA, Madsen HO, Tarp U, Svejgaard A, Jurik G, Graudal HK, Garred P (2000) The association of variant mannose-binding lectin genotypes with radiographic outcome in rheumatoid arthritis. Arthritis Rheum 43:515–521
Aydin SZ, Atagunduz P, Erer B, Bahadir C, Inanc N, Direskeneli H (2010) Mannose binding lectin levels are not related to radiographic damage in ankylosing spondylitis. Rheumatol Int 30:415–417
Brown MA, Pile KD, Kennedy LG, Campbell D, Andrew L, March R, Shatford JL, Weeks DE, Calin A, Wordsworth BP (1998) A genome-wide screen for susceptibility loci in ankylosing spondylitis. Arthritis Rheum 41:588–595
Laval SH, Timms A, Edwards S, Bradbury L, Brophy S, Milicic A, Rubin L, Siminovitch KA, Weeks DE, Calin A, Wordsworth BP, Brown MA (2001) Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci. Am J Hum Genet 68:918–926
Gu MM, Yuan WT, Yang JQ, Zhang J, Xiong XY, Yao FJ, Lu ZY, Wang ZG, Huang W, Fan LA (2004) A genomewide scan for the susceptibility gene loci to ankylosing spondylitis in Chinese Han population. Yi Chuan Xue Bao 31:217–220
Zhang G, Luo J, Bruckel J, Weisman MA, Schumacher HR, Khan MA, Inman RD, Mahowald M, Maksymowych WP, Martin TM, Yu DT, Stone M, Rosenbaum JT, Newman P, Lee J, McClain JA, West OC, Jin L, Reveille JD (2004) Genetic studies in familial ankylosing spondylitis susceptibility. Arthritis Rheum 50:2246–2254
Carter KW, Pluzhnikov A, Timms AE, Miceli-Richard C, Bourgain C, Wordsworth BP, Jean-Pierre H, Cox NJ, Palmer LJ, Breban M, Reveille JD, Brown MA (2007) Combined analysis of three whole genome linkage scans for ankylosing spondylitis. Rheumatology (Oxford) 46:763–771
Huang J, Li C, Xu H, Gu J (2008) Novel non-HLA-susceptible regions determined by meta-analysis of four genomewide scans for ankylosing spondylitis. J Genet 87:75–81
van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368
Tsutsumi A, Sasaki K, Wakamiya N, Ichikawa K, Atsumi T, Ohtani K, Suzuki Y, Koike T, Sumida T (2001) Mannose-binding lectin gene: polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren’s syndrome. Genes Immun 2:99–104
Steffensen R, Thiel S, Varming K, Jersild C, Jensenius JC (2000) Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers. J Immunol Methods 241:33–42
Madsen HO, Garred P, Kurtzhals JA, Lamm LU, Ryder LP, Thiel S, Svejgaard A (1994) A new frequent allele is the missing link in the structural polymorphisms of the human mannan-binding protein. Immunogenetics 40:37–44
Matsushita M, Hijikata M, Ohta Y, Iwata K, Matsumoto M, Nakao K, Kanai K, Yoshida N, Baba K, Mishiro S (1998) Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL. Arch Virol 143:645–651
Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265
Jacobsen S, Garred P, Madsen HO, Heegaard NH, Hetland ML, Stengaard-Pedersen K, Junker P, Lottenburger T, Ellingsen T, Smedegaar Anderson L, Hansen I, Skjodt H, Pedersen JK, Lauridsen UB, Svendsen AJ, Trap U, Podenphant J, Lindegaard H, Vestergaard A, Ostergaard M, Horslev-Petersen K (2009) Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis. J Rheumatol 36:731–735
Stanworth SJ, Donn RP, Hassall A, Dawes P, Ollier W, Snowden N (1998) Absence of an association between mannose-binding lectin polymorphism and rheumatoid arthritis. Br J Rheumatol 37:186–188
van de Geijn FE, Hazes JM, Geleijns K, Emonts M, Jacobs BC, Dufour-van den Goorbergh BC, Dolhain RJ (2008) Mannose-binding lectin polymorphisms are not associated with rheumatoid arthritis - confirmation in two large cohorts. Rheumatology (Oxford) 47:1168–1171
Gergely P Jr, Pazár B, Nagy ZB, Gombos T, Rajczy K, Balogh Z, Obran I, Sevicic K, Poor G (2009) Structural polymorphisms in the mannose-binding lectin gene are associated with juvenile idiopathic arthritis. J Rheumatol 36:843–847
Dahl MR, Thiel S, Matsushita M, Fujita T, Willis AC, Christensen T, Vorup-Jensen T, Jensenius JC (2001) MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 15:127–135
Jack DL, Read RC, Tenner AJ, Frosch M, Turner MW, Klein NJ (2001) Mannose-binding lectin regulates the inflammatory response of human professional phagocytes to Neisseria meningitidis serogroup B. J Infect Dis 184:1152–1162
Ip WK, Takahashi K, Moore KJ, Stuart LM, Ezekowitz RA (2008) Mannose-binding lectin enhances toll-like receptors 2 and 6 signaling from the phagosome. J Exp Med 205:169–181
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This study was supported by a grant from Seoul National University.
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Im, C.H., Kim, J., Lee, Y.J. et al. Mannose-binding lectin 2 gene haplotype analysis in Korean patients with ankylosing spondylitis. Rheumatol Int 32, 2251–2255 (2012). https://doi.org/10.1007/s00296-011-1939-2
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DOI: https://doi.org/10.1007/s00296-011-1939-2