Abstract
Psoriasis, an inflammatory skin disease, was associated with a promoter variant (rs9267502; P = 3.786 × 10−19) of LST1 that may regulate immune response and cellular morphogenesis. Promoter activity was examined to identify functional variants in the proximity of the associated variant. Five natural haplotypes (H1–H5) of four variants (rs7758790, rs9267502, rs41268884, rs17200775) in strong linkage disequilibrium were investigated. The most common haplotype (H1) was TGAG (frequency 0.78), and the second most frequent haplotype (H2) was CGGG (0.09). Luciferase assay was conducted using reporter constructs including each haplotype and firefly luciferase gene. As a result, promoter activity of H1 was smaller than the construct without the promoter region (P < 0.05). The promoter activities of H3, H4, and H5 corresponded to that of H1 (P > 0.05), and H2 promoter activity was larger than that of H1, H3, H4, and H5 (P < 0.05). This might result from changes in binding affinity to transcription factors by nucleotide substitutions of the promoter variants of the LST1 gene.
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References
Al-Alwan MM, Rowden G, Lee TD, West KA (2001) Fascin is involved in the antigen presentation activity of mature dendritic cells. J Immunol 166:338–345
Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811
Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265
Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY, Sack MN, Kastner DL, Siegel RM (2011) Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med 208:519–533
Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80:273–290
Chandran V, Raychaudhuri SP (2010) Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 34:J314–J321
Dickie LJ, Aziz AM, Savic S, Lucherini OM, Cantarini L, Geiler J, Wong CH, Coughlan R, Lane T, Lachmann HJ, Hawkins PN, Robinson PA, Emery P, McGonagle D, McDermott MF (2012) Involvement of X-box binding protein 1 and reactive oxygen species pathways in the pathogenesis of tumour necrosis factor receptor-associated periodic syndrome. Ann Rheum Dis 71:2035–2043
Ellinghaus E, Ellinghaus D, Stuart PE, Nair RP, Debrus S, Raelson JV, Belouchi M, Fournier H, Reinhard C, Ding J, Li Y, Tejasvi T, Gudjonsson J, Stoll SW, Voorhees JJ, Lambert S, Weidinger S, Eberlein B, Kunz M, Rahman P, Gladman DD, Gieger C, Wichmann HE, Karlsen TH, Mayr G, Albrecht M, Kabelitz D, Mrowietz U, Abecasis GR, Elder JT, Schreiber S, Weichenthal M, Franke A (2010) Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet 42:991–995
Lacroix M, Leclercq G (2004) About GATA3, HNF3A, and XBP1, three genes co-expressed with the oestrogen receptor-alpha gene (ESR1) in breast cancer. Mol Cell Endocrinol 219:1–7
Lebwohl M (2003) Psoriasis. Lancet 361:1197–1204
Manolio TA, Rodriguez LL, Brooks L, Abecasis G, Ballinger D, Daly M, Donnelly P, Faraone SV, Frazer K, Gabriel S, Gejman P, Guttmacher A, Harris EL, Insel T, Kelsoe JR, Lander E, McCowin N, Mailman MD, Nabel E, Ostell J, Pugh E, Sherry S, Sullivan PF, Thompson JF, Warram J, Wholley D, Milos PM, Collins FS (2007) New models of collaboration in genomewide association studies: the genetic association information network. Nat Genet 39:1045–1051
Messeguer X, Escudero R, Farré D, Núñez O, Martínez J, Albà MM (2002) PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics 18:333–334
Mulcahy H, O’Rourke KP, Adams C, Molloy MG, O’Gara F (2006) LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-gamma, LPS and microbial infection. Immunogenetics 57:893–903
Park SH, Chi HS, Cho YU, Jang S, Park CJ (2013) CEBPA single mutation can be a possible favorable prognostic indicator in NPM1 and FLT3-ITD wild-type acute myeloid leukemia patients with intermediate cytogenetic risk. Leuk Res 37:1488–1494
Raghunathan A, Sivakamasundari R, Wolenski J, Poddar R, Weissman SM (2001) Functional analysis of B144/LST1: a gene in the tumor necrosis factor cluster that induces formation of long filopodia in eukaryotic cells. Exp Cell Res 268:230–244
Savic S, Ouboussad L, Dickie LJ, Geiler J, Wong C, Doody GM, Churchman SM, Ponchel F, Emery P, Cook GP, Buch MH, Tooze RM, McDermott MF (2013) TLR dependent XBP-1 activation induces an autocrine loop in rheumatoid arthritis synoviocytes. J Autoimmun. doi:10.1016/j.jaut.2013.11.002
Trembath RC, Clough RL, Rosbotham JL, Jones AB, Camp RD, Frodsham A, Browne J, Barber R, Terwilliger J, Lathrop GM, Barker JN (1997) Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum Mol Genet 6:813–820
Yu X, Weissman SM (2000) Characterization of the promoter of human leukocyte-specific transcript 1: a small gene with a complex pattern of alternative transcripts. J Biol Chem 275:34597–34608
Zhang XJ, Huang W, Yang S, Sun LD, Zhang FY, Zhu QX, Zhang FR, Zhang C, Du WH, Pu XM, Li H, Xiao FL, Wang ZX, Cui Y, Hao F, Zheng J, Yang XQ, Cheng H, He CD, Liu XM, Xu LM, Zheng HF, Zhang SM, Zhang JZ, Wang HY, Cheng YL, Ji BH, Fang QY, Li YZ, Zhou FS, Han JW, Quan C, Chen B, Liu JL, Lin D, Fan L, Zhang AP, Liu SX, Yang CJ, Wang PG, Zhou WM, Lin GS, Wu WD, Fan X, Gao M, Yang BQ, Lu WS, Zhang Z, Zhu KJ, Shen SK, Li M, Zhang XY, Cao TT, Ren W, Zhang X, He J, Tang XF, Lu S, Yang JQ, Zhang L, Wang DN, Yuan F, Yin XY, Huang HJ, Wang HF, Lin XY, Liu JJ (2009) Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 41:205–210
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This study was supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science, and Technology (Grant No. 2012002096).
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Woo, J., Lee, C. Identification of Functional Haplotypes in the Promoter Region of the LST1 Gene. Biochem Genet 52, 365–371 (2014). https://doi.org/10.1007/s10528-014-9653-x
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DOI: https://doi.org/10.1007/s10528-014-9653-x