Targeted Resequencing and Functional Testing Identifies Low-Frequency Missense Variants in the Gene Encoding GARP as Significant Contributors to Atopic Dermatitis Risk

Journal of Investigative Dermatology

Volumn 136, Issue 12, 2016, Pages 2380-2386

  Manz, Judith ^a   Rodríguez, Elke ^b   ElSharawy, Abdou ^c,d   Oesau, Eva Maria ^e   Petersen, Britt Sabina ^c   Baurecht, Hansjörg ^b   Mayr, Gabriele ^c   Weber, Susanne ^a   Harder, Jürgen ^b   Reischl, Eva ^a   Schwarz, Agatha ^b   Novak, Natalija ^e   Franke, Andre ^c   Weidinger, Stephan ^b  

^a INSTITUTE OF EPIDEMIOLOGY   (Germany)

^b UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^c UNIVERSITY OF KIEL   (Germany)

^d Damietta University   (Egypt)

^e UNIVERSITY HOSPITAL BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; GARP PROTEIN; INTERLEUKIN 2 RECEPTOR ALPHA; LATENCY ASSOCIATED PEPTIDE; RECEPTOR PROTEIN; SPACER DNA; STRUCTURAL PROTEIN; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; LRRC32 PROTEIN, HUMAN; MEMBRANE PROTEIN; MESSENGER RNA;

ARTICLE; ATOPIC DERMATITIS; C11ORF30 GENE; CD4+ CD25+ T LYMPHOCYTE; CHROMOSOME 11Q; CHROMOSOME BAND; CONTROLLED STUDY; FLOW CYTOMETRY; GENE; GENE FREQUENCY; GENE LOCUS; GENE MAPPING; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; HUMAN CELL; LRRC32 GENE; MISSENSE MUTATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TRANSPORT; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; T LYMPHOCYTE SUBPOPULATION; ADULT; CASE CONTROL STUDY; CELL CULTURE; CHROMOSOMAL MAPPING; COMPARATIVE STUDY; DERMATITIS, ATOPIC; DISEASE COURSE; FEMALE; GENE DELETION; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION; GENETICS; GENOTYPE; IMMUNOHISTOCHEMISTRY; IMMUNOLOGY; MALE; MOLECULAR GENETICS; PATHOLOGY; PROGNOSIS; REAL TIME POLYMERASE CHAIN REACTION; RISK ASSESSMENT;

ADULT; CASE-CONTROL STUDIES; CELLS, CULTURED; CHROMOSOME MAPPING; DERMATITIS, ATOPIC; DISEASE PROGRESSION; FEMALE; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; IMMUNOHISTOCHEMISTRY; MALE; MEMBRANE PROTEINS; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; PROGNOSIS; REAL-TIME POLYMERASE CHAIN REACTION; RISK ASSESSMENT; RNA, MESSENGER; SEQUENCE DELETION; T-LYMPHOCYTES, REGULATORY;

EID: 84997530265     PISSN: 0022202X     EISSN: 15231747     Source Type: Journal    
DOI: 10.1016/j.jid.2016.07.009     Document Type: Article

References (34)

1. Anderson, C.A., Boucher, G., Lees, C.W., Franke, A., D'Amato, M., Taylor, K.D., et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43 (2011), 246–252.
2. Banchereau, J., Pascual, V., O'Garra, A., From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol 13 (2012), 925–931.
3. Barrett, J.C., Hansoul, S., Nicolae, D.L., Cho, J.H., Duerr, R.H., Rioux, J.D., et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 40 (2008), 955–962.
4. Betz, R.C., Petukhova, L., Ripke, S., Huang, H., Menelaou, A., Redler, S., et al. Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci. Nat Commun, 6, 2015, 5966.
5. Bonnelykke, K., Matheson, M.C., Pers, T.H., Granell, R., Strachan, D.P., Alves, A.C., et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat Genet 45 (2013), 902–906.
6. Chen, R., Jiang, X., Sun, D., Han, G., Wang, F., Ye, M., et al. Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res 8 (2009), 651–661.
7. Cuende, J., Lienart, S., Dedobbeleer, O., van der Woning, B., De Boeck, G., Stockis, J., et al. Monoclonal antibodies against GARP/TGF-beta1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo. Sci Transl Med, 7, 2015, 284ra56.
8. Edwards, J.P., Fujii, H., Zhou, A.X., Creemers, J., Unutmaz, D., Shevach, E.M., Regulation of the expression of GARP/latent TGF-beta1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation. J Immunol 190 (2013), 5506–5515.
9. Ellinghaus, D., Baurecht, H., Esparza-Gordillo, J., Rodriguez, E., Matanovic, A., Marenholz, I., et al. High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat Genet 45 (2013), 808–812.
10. Esparza-Gordillo, J., Weidinger, S., Folster-Holst, R., Bauerfeind, A., Ruschendorf, F., Patone, G., et al. A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat Genet 41 (2009), 596–601.
11. Ezell, S.A., Polytarchou, C., Hatziapostolou, M., Guo, A., Sanidas, I., Bihani, T., et al. The protein kinase Akt1 regulates the interferon response through phosphorylation of the transcriptional repressor EMSY. Proc Natl Acad Sci USA 109 (2012), E613–E621.
12. Ferreira, M.A., Matheson, M.C., Duffy, D.L., Marks, G.B., Hui, J., Le Souef, P., et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 378 (2011), 1006–1014.
13. Franke, A., McGovern, D.P., Barrett, J.C., Wang, K., Radford-Smith, G.L., Ahmad, T., et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 42 (2010), 1118–1125.
14. Frischmeyer-Guerrerio, P.A., Guerrerio, A.L., Oswald, G., Chichester, K., Myers, L., Halushka, M.K., et al. TGFbeta receptor mutations impose a strong predisposition for human allergic disease. Sci Transl Med, 5, 2013, 195ra94.
15. Garapaty, S., Xu, C.F., Trojer, P., Mahajan, M.A., Neubert, T.A., Samuels, H.H., Identification and characterization of a novel nuclear protein complex involved in nuclear hormone receptor-mediated gene regulation. J Biol Chem 284 (2009), 7542–7552.
16. Gulick, T., Transfection using DEAE-dextran. Curr Protoc Mol Biol, 2001 Chapter 9:Unit 9.2.
17. Hahn, S.A., Stahl, H.F., Becker, C., Correll, A., Schneider, F.J., Tuettenberg, A., et al. Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4(+) T cells. Blood 122 (2013), 1182–1191.
18. The International Genome Sample Resource. ISGR: The International Genome Sample Resource, http://www.1000genomes.org/; 2016 (accessed 28 July 2016).
19. Johansson, H., Isaksson, M., Sorqvist, E.F., Roos, F., Stenberg, J., Sjoblom, T., et al. Targeted resequencing of candidate genes using selector probes. Nucleic Acids Res, 39, 2010, e8.
20. Kottyan, L.C., Davis, B.P., Sherrill, J.D., Liu, K., Rochman, M., Kaufman, K., et al. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat Genet 46 (2014), 895–900.
21. Krawczak, M., Nikolaus, S., von Eberstein, H., Croucher, P.J., El Mokhtari, N.E., Schreiber, S., PopGen: population-based recruitment of patients and controls for the analysis of complex genotype-phenotype relationships. Community Genet 9 (2006), 55–61.
22. National Center for Biotechnology Information. dbSNP Short Genetic Variations, http://www.ncbi.nlm.nih.gov/SNP/; 2016 (accessed 28 July 2016).
23. Paternoster, L., Standl, M., Chen, C.M., Ramasamy, A., Bonnelykke, K., Duijts, L., et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet 44 (2012), 187–192.
24. Paternoster, L., Standl, M., Waage, J., Baurecht, H., Hotze, M., Strachan, D.P., et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet 47 (2015), 1449–1456.
25. Probst-Kepper, M., Geffers, R., Kroger, A., Viegas, N., Erck, C., Hecht, H.J., et al. GARP: a key receptor controlling FOXP3 in human regulatory T cells. J Cell Mol Med 13 (2009), 3343–3357.
26. R Development Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, http://www.R-project.org; 2008 (accessed 28 July 2016).
27. Ramasamy, A., Curjuric, I., Coin, L.J., Kumar, A., McArdle, W.L., Imboden, M., et al. A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J Allergy Clin Immunol 128 (2011), 996–1005.
28. Roth, S.A., Simanski, M., Rademacher, F., Schroder, L., Harder, J., The pattern recognition receptor NOD2 mediates Staphylococcus aureus-induced IL-17C expression in keratinocytes. J Invest Dermatol 134 (2014), 374–380.
29. Tran, D.Q., Andersson, J., Wang, R., Ramsey, H., Unutmaz, D., Shevach, E.M., GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. Proc Natl Acad Sci USA 106 (2009), 13445–13450.
30. Wang, R., Kozhaya, L., Mercer, F., Khaitan, A., Fujii, H., Unutmaz, D., Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells. Proc Natl Acad Sci USA 106 (2009), 13439–13444.
31. Wang, R., Zhu, J., Dong, X., Shi, M., Lu, C., Springer, T.A., GARP regulates the bioavailability and activation of TGFbeta. Mol Biol Cell 23 (2012), 1129–1139.
32. Weidinger, S., Novak, N., Atopic dermatitis. Lancet 387 (2016), 1109–1122.
33. Weidinger, S., Willis-Owen, S.A., Kamatani, Y., Baurecht, H., Morar, N., Liang, L., et al. A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. Hum Mol Genet 22 (2013), 4841–4856.
34. Zawistowski, M., Gopalakrishnan, S., Ding, J., Li, Y., Grimm, S., Zollner, S., Extending rare-variant testing strategies: analysis of noncoding sequence and imputed genotypes. Am J Hum Genet 87 (2010), 604–617.