Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

被引:54
作者
Bossini-Castillo, Lara [1 ]
Lopez-Isac, Elena [1 ]
Martin, Javier [1 ]
机构
[1] CSIC, IPBLN, Granada, Spain
关键词
Systemic sclerosis; Genetics; Polymorphism; Heritability; Shared loci; GENOME-WIDE ASSOCIATION; GENETIC RISK-FACTOR; INTERLEUKIN-12/23; MONOCLONAL-ANTIBODY; HUMAN-LEUKOCYTE ANTIGENS; PPAR-GAMMA GENE; SUSCEPTIBILITY LOCI; INDEPENDENT REPLICATION; LUPUS-ERYTHEMATOSUS; CANDIDATE GENE; DOUBLE-BLIND;
D O I
10.1016/j.jaut.2015.07.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Systemic sclerosis (SSc) is a clinically heterogeneous connective tissue disorder of complex etiology. The development of large-scale genetic studies, such as genome-wide association studies (GWASs) or the Immunochip platform, has achieved remarkable progress in the knowledge of the genetic background of SSc. Herein, we provide an updated picture SSc genetic factors, offering an insight into their role in pathogenic mechanisms that characterize the disease. We review the most recent findings in the HLA region and the well-established non-HLA loci. Up to 18 non-HLA risk factors fulfilled the selected criteria and they were classified according to their role in the innate or adaptive immune response, in apoptosis, autophagy or fibrosis. Additionally, SSc heritability has remained as a controversial question since twin studies provided low SSc heritability estimates. However, we have recalculated the lower bond of narrow sense SSc heritability using GWAS data. Remarkably, our results suggest a greater influence of genetics on SSc than previously reported. Furthermore, we also offer a functional classification of SSc-associated SNPs and their proxies, based on annotated data, to provide clues for the identification of causal variants in these lad. Finally, we explore the genetic overlap between SSc and other autoimmune diseases (ADs). The vast majority of SSc risk loci are shared with at least one additional AD, being the overlap between SSc and systemic lupus erythematous the largest. Nevertheless, we found that an important portion of SSc risk factors are also common to rheumatoid arthritis or primary biliary cirrhosis. Considering all these evidences, we are confident that future research will be successful in understanding the relevant altered pathways in SSc and in identifying new biomarkers and therapeutic targets for the disease. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:53 / 65
页数:13
相关论文
共 147 条
[1]   Identification of a functional estrogen-responsive enhancer element in the promoter 2 of PRDM2 gene in breast cancer cell lines [J].
Abbondanza, Ciro ;
De Rosa, Caterina ;
D'Arcangelo, Andrea ;
Pacifico, Marianna ;
Spizuoco, Clorinda ;
Piluso, Giulio ;
Di Zazzo, Erika ;
Gazzerro, Patrizia ;
Medici, Nicola ;
Moncharmont, Bruno ;
Puca, Giovanni Alfredo .
JOURNAL OF CELLULAR PHYSIOLOGY, 2012, 227 (03) :964-975
[2]   Overview of pathogenesis of systemic sclerosis [J].
Abraham, D. J. ;
Krieg, T. ;
Distler, J. ;
Distler, O. .
RHEUMATOLOGY, 2009, 48 :3-7
[3]   Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus [J].
Al-Mayouf, Sulaiman M. ;
Sunker, Asma ;
Abdwani, Reem ;
Al Abrawi, Safiya ;
Almurshedi, Fathiya ;
Alhashmi, Nadia ;
Al Sonbul, Abdullah ;
Sewairi, Wafaa ;
Qari, Aliya ;
Abdallah, Eiman ;
Al-Owain, Mohammed ;
Al Motywee, Saleh ;
Al-Rayes, Hanan ;
Hashem, Mais ;
Khalak, Hanif ;
Al-Jebali, Latifa ;
Alkuraya, Fowzan S. .
NATURE GENETICS, 2011, 43 (12) :1186-1188
[4]   Genome-Wide Scan Identifies TNIP1, PSORS1C1, and RHOB As Novel Risk Loci for Systemic Sclerosis [J].
Allanore, Yannick ;
Saad, Mohamad ;
Dieude, Philippe ;
Avouac, Jerome ;
Distler, Jorg H. W. ;
Amouyel, Philippe ;
Matucci-Cerinic, Marco ;
Riemekasten, Gabriella ;
Airo, Paolo ;
Melchers, Inga ;
Hachulla, Eric ;
Cusi, Daniele ;
Wichmann, H. -Erich ;
Wichmann, Erich ;
Wipff, Julien ;
Lambert, Jean-Charles ;
Hunzelmann, Nicolas ;
Tiev, Kiet ;
Caramaschi, Paola ;
Diot, Elisabeth ;
Kowal-Bielecka, Otylia ;
Valentini, Gabriele ;
Mouthon, Luc ;
Czirjak, Laszlo ;
Damjanov, Nemanja ;
Salvi, Erika ;
Conti, Costanza ;
Mueller, Martina ;
Mueller-Ladner, Ulf ;
Riccieri, Valeria ;
Ruiz, Barbara ;
Cracowski, Jean-Luc ;
Letenneur, Luc ;
Dupuy, Anne Marie ;
Meyer, Oliver ;
Kahan, Andre ;
Munnich, Arnold ;
Boileau, Catherine ;
Martinez, Maria .
PLOS GENETICS, 2011, 7 (07)
[5]   Sex differences and genomics in autoimmune diseases [J].
Amur, Shashi ;
Parekh, Ameeta ;
Mummaneni, Padmaja .
JOURNAL OF AUTOIMMUNITY, 2012, 38 (2-3) :J254-J265
[6]  
[Anonymous], ANN RHEUM DIS
[7]   Identification of NF-κB and PLCL2 as new susceptibility genes and highlights on a potential role of IRF8 through interferon signature modulation in systemic sclerosis [J].
Arismendi, Maria ;
Giraud, Matthieu ;
Ruzehaji, Nadira ;
Dieude, Philippe ;
Koumakis, Eugenie ;
Ruiz, Barbara ;
Airo, Paolo ;
Cusi, Daniele ;
Matucci-Cerinic, Marco ;
Salvi, Erika ;
Cuomo, Giovanna ;
Hachulla, Eric ;
Diot, Elisabeth ;
Caramaschi, Paola ;
Riccieri, Valeria ;
Avouac, Jerome ;
Kayser, Cristiane ;
Allanore, Yannick .
ARTHRITIS RESEARCH & THERAPY, 2015, 17
[8]   Increased prevalence of systemic sclerosis in a native American tribe in Oklahoma - Association with an Amerindian HLA haplotype [J].
Arnett, FC ;
Howard, RF ;
Tan, FM ;
Moulds, JM ;
Bias, WB ;
Durban, E ;
Cameron, HD ;
Paxton, G ;
Hodge, TJ ;
Weathers, PE ;
Reveille, JD .
ARTHRITIS AND RHEUMATISM, 1996, 39 (08) :1362-1370
[9]   Major histocompatibility complex (MHC) class II alleles, haplotypes and epitopes which confer susceptibility or protection in systemic sclerosis: analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls [J].
Arnett, Frank C. ;
Gourh, Pravitt ;
Shete, Sanjay ;
Ahn, Chul W. ;
Honey, Robert E. ;
Agarwal, Sandeep K. ;
Tan, Filemon K. ;
McNearney, Terry ;
Fischbach, Michael ;
Fritzler, Marvin J. ;
Mayes, Maureen D. ;
Reveille, John D. .
ANNALS OF THE RHEUMATIC DISEASES, 2010, 69 (05) :822-827
[10]   Autoimmune diseases and autoantibodies in the first degree relatives of patients with systemic sclerosis [J].
Arora-Singh, Rajpreet K. ;
Assassi, Shervin ;
del Junco, Deborah J. ;
Arnett, Frank C. ;
Perry, Marilyn ;
Irfan, Uzma ;
Sharif, Roozbeh ;
Mattar, Tony ;
Mayes, Maureen D. .
JOURNAL OF AUTOIMMUNITY, 2010, 35 (01) :52-57