Genetics of Systemic Sclerosis: An Update

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go back to reference Frech T, Khanna D, Markewitz B, Mineau G, Pimentel R, Sawitzke A. Heritability of vasculopathy, autoimmune disease, and fibrosis in systemic sclerosis: a population-based study. Arthritis Rheum. 2010;62(7):2109–16.PubMed Frech T, Khanna D, Markewitz B, Mineau G, Pimentel R, Sawitzke A. Heritability of vasculopathy, autoimmune disease, and fibrosis in systemic sclerosis: a population-based study. Arthritis Rheum. 2010;62(7):2109–16.PubMed

go back to reference Arora-Singh RK, Assassi S, del Junco DJ, Arnett FC, Perry M, Irfan U, Sharif R, Mattar T, Mayes MD. Autoimmune diseases and autoantibodies in the first degree relatives of patients with systemic sclerosis. J Autoimmun. 2010;35(1):52–7. Epub 2010 Mar 11.PubMedCrossRef Arora-Singh RK, Assassi S, del Junco DJ, Arnett FC, Perry M, Irfan U, Sharif R, Mattar T, Mayes MD. Autoimmune diseases and autoantibodies in the first degree relatives of patients with systemic sclerosis. J Autoimmun. 2010;35(1):52–7. Epub 2010 Mar 11.PubMedCrossRef

go back to reference • Cockrill T, del Junco DJ, Arnett FC, Assassi S, Tan FK, McNearney T, Fischbach M, Perry M, Mayes MD. Separate influences of birth order and gravidity/parity on the development of systemic sclerosis. Arthritis Care Res (Hoboken). 2010 Mar;62(3):418–24. This study is interesting because it points to the existence of mechanisms involved in determining SSc susceptibility during embryonic development or birth. • Cockrill T, del Junco DJ, Arnett FC, Assassi S, Tan FK, McNearney T, Fischbach M, Perry M, Mayes MD. Separate influences of birth order and gravidity/parity on the development of systemic sclerosis. Arthritis Care Res (Hoboken). 2010 Mar;62(3):418–24. This study is interesting because it points to the existence of mechanisms involved in determining SSc susceptibility during embryonic development or birth.

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go back to reference Rueda B, Broen J, Simeon C, Hesselstrand R, Diaz B, Suárez H, Ortego-Centeno N, Riemekasten G, Fonollosa V, Vonk MC, van den Hoogen FH, Sanchez-Román J, Aguirre-Zamorano MA, García-Portales R, Pros A, Camps MT, Gonzalez-Gay MA, Coenen MJ, Airo P, Beretta L, Scorza R, van Laar J, Gonzalez-Escribano MF, Nelson JL, Radstake TR, Martin J. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum Mol Genet. 2009;18(11):2071–7. Epub 2009 Mar 13.PubMedCrossRef Rueda B, Broen J, Simeon C, Hesselstrand R, Diaz B, Suárez H, Ortego-Centeno N, Riemekasten G, Fonollosa V, Vonk MC, van den Hoogen FH, Sanchez-Román J, Aguirre-Zamorano MA, García-Portales R, Pros A, Camps MT, Gonzalez-Gay MA, Coenen MJ, Airo P, Beretta L, Scorza R, van Laar J, Gonzalez-Escribano MF, Nelson JL, Radstake TR, Martin J. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum Mol Genet. 2009;18(11):2071–7. Epub 2009 Mar 13.PubMedCrossRef

go back to reference Tsuchiya N, Kawasaki A, Hasegawa M, Fujimoto M, Takehara K, Kawaguchi Y, Kawamoto M, Hara M, Sato S. Association of STAT4 polymorphism with systemic sclerosis in a Japanese population. Ann Rheum Dis. 2009;68(8):1375–6.PubMedCrossRef Tsuchiya N, Kawasaki A, Hasegawa M, Fujimoto M, Takehara K, Kawaguchi Y, Kawamoto M, Hara M, Sato S. Association of STAT4 polymorphism with systemic sclerosis in a Japanese population. Ann Rheum Dis. 2009;68(8):1375–6.PubMedCrossRef

go back to reference Dieudé P, Guedj M, Wipff J, Ruiz B, Hachulla E, Diot E, Granel B, Sibilia J, Tiev K, Mouthon L, Cracowski JL, Carpentier PH, Amoura Z, Fajardy I, Avouac J, Meyer O, Kahan A, Boileau C, Allanore Y. STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis. Arthritis Rheum. 2009;60(8):2472–9.PubMedCrossRef Dieudé P, Guedj M, Wipff J, Ruiz B, Hachulla E, Diot E, Granel B, Sibilia J, Tiev K, Mouthon L, Cracowski JL, Carpentier PH, Amoura Z, Fajardy I, Avouac J, Meyer O, Kahan A, Boileau C, Allanore Y. STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis. Arthritis Rheum. 2009;60(8):2472–9.PubMedCrossRef

go back to reference Gourh P, Agarwal SK, Divecha D, Assassi S, Paz G, Arora-Singh RK, Reveille JD, Shete S, Mayes MD, Arnett FC, Tan FK. Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: evidence of possible gene-gene interaction and alterations in Th1/Th2 cytokines. Arthritis Rheum. 2009;60(12):3794–806.PubMedCrossRef Gourh P, Agarwal SK, Divecha D, Assassi S, Paz G, Arora-Singh RK, Reveille JD, Shete S, Mayes MD, Arnett FC, Tan FK. Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: evidence of possible gene-gene interaction and alterations in Th1/Th2 cytokines. Arthritis Rheum. 2009;60(12):3794–806.PubMedCrossRef

go back to reference • Avouac J, Fürnrohr BG, Tomcik M, Palumbo K, Zerr P, Horn A, Dees C, Akhmetshina A, Beyer C, Distler O, Schett G, Allanore Y, Distler JH. Inactivation of the transcription factor STAT4 prevents inflammation-driven fibrosis in systemic sclerosis animal models. Arthritis Rheum. 2010 Nov 30. [Epub ahead of print]. This was an interesting study as it investigated for the first time a gene strongly implicated in SSc susceptibility, STAT4, in a murine model of SSc. • Avouac J, Fürnrohr BG, Tomcik M, Palumbo K, Zerr P, Horn A, Dees C, Akhmetshina A, Beyer C, Distler O, Schett G, Allanore Y, Distler JH. Inactivation of the transcription factor STAT4 prevents inflammation-driven fibrosis in systemic sclerosis animal models. Arthritis Rheum. 2010 Nov 30. [Epub ahead of print]. This was an interesting study as it investigated for the first time a gene strongly implicated in SSc susceptibility, STAT4, in a murine model of SSc.

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go back to reference Dieudé P, Guedj M, Truchetet ME, Wipff J, Revillod L, Riemekasten G, Matucci-Cerinic M, Melchers I, Hachulla E, Airo P, Diot E, Hunzelmann N, Mouthon L, Cabane J, Cracowski JL, Riccieri V, Distler J, Amoura Z, Valentini G, Camaraschi P, Tarner I, Frances C, Carpentier P, Brembilla NC, Meyer O, Kahan A, Chizzolini C, Boileau C, Allanore Y. Association of the CD226 Ser(307) variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis. Arthritis Rheum. 2011;63(4):1097–105. doi:10.1002/art.30204.PubMedCrossRef Dieudé P, Guedj M, Truchetet ME, Wipff J, Revillod L, Riemekasten G, Matucci-Cerinic M, Melchers I, Hachulla E, Airo P, Diot E, Hunzelmann N, Mouthon L, Cabane J, Cracowski JL, Riccieri V, Distler J, Amoura Z, Valentini G, Camaraschi P, Tarner I, Frances C, Carpentier P, Brembilla NC, Meyer O, Kahan A, Chizzolini C, Boileau C, Allanore Y. Association of the CD226 Ser(307) variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis. Arthritis Rheum. 2011;63(4):1097–105. doi:10.​1002/​art.​30204.PubMedCrossRef

go back to reference Alizadeh BZ, Broen J, Rueda B, Hesselstrand R, Wuttge D, Simeon C, Ortego-Centeno N, Gonzalez-Gay MA, Pros A, Herrick A, Worthington J, Denton C, Fonseca C, Riemekasten G, Vonk MC, van den Hoogen F, Guiducci S, Matucci-Cerinic M, Scorza R, Beretta L, Airó P, Coenen M, Martin J, Koeleman BP, Radstake TR, EUSTAR. Functional variants of Fc gamma receptor (FCGR2A) and FCGR3A are not associated with susceptibility to systemic sclerosis in a large European Study (EUSTAR). J Rheumatol. 2010;37(8):1673–9. Epub 2010 Jun 15.PubMedCrossRef Alizadeh BZ, Broen J, Rueda B, Hesselstrand R, Wuttge D, Simeon C, Ortego-Centeno N, Gonzalez-Gay MA, Pros A, Herrick A, Worthington J, Denton C, Fonseca C, Riemekasten G, Vonk MC, van den Hoogen F, Guiducci S, Matucci-Cerinic M, Scorza R, Beretta L, Airó P, Coenen M, Martin J, Koeleman BP, Radstake TR, EUSTAR. Functional variants of Fc gamma receptor (FCGR2A) and FCGR3A are not associated with susceptibility to systemic sclerosis in a large European Study (EUSTAR). J Rheumatol. 2010;37(8):1673–9. Epub 2010 Jun 15.PubMedCrossRef

go back to reference Coustet B, Agarwal SK, Gourh P, Guedj M, Mayes MD, Dieude P, Wipff J, Avouac J, Hachulla E, Diot E, Cracowski JL, Tiev K, Sibilia J, Mouthon L, Frances C, Amoura Z, Carpentier P, Meyer O, Kahan A, Boileau C, Arnett FC, Allanore Y. Association study of ITGAM, ITGAX, and CD58 autoimmune risk loci in systemic sclerosis: results from 2 large European Caucasian cohorts. J Rheumatol. 2011 Mar 1. [Epub ahead of print]. Coustet B, Agarwal SK, Gourh P, Guedj M, Mayes MD, Dieude P, Wipff J, Avouac J, Hachulla E, Diot E, Cracowski JL, Tiev K, Sibilia J, Mouthon L, Frances C, Amoura Z, Carpentier P, Meyer O, Kahan A, Boileau C, Arnett FC, Allanore Y. Association study of ITGAM, ITGAX, and CD58 autoimmune risk loci in systemic sclerosis: results from 2 large European Caucasian cohorts. J Rheumatol. 2011 Mar 1. [Epub ahead of print].

go back to reference Broen JC, Coenen MJ, Rueda B, Witte T, Padyukov L, Klareskog L, Hesselstrand R, Wuttge DM, Simeon C, Ortego-Centeno N, González-Gay MA, Pros A, Hunzelman N, Riemekasten G, Kreuter A, Vonk M, Scorza R, Beretta L, Airò P, van Riel PL, Kimberly R, Martin J, Edberg J, Radstake TR. The functional polymorphism 844 A>G in FcαRI (CD89) does not contribute to systemic sclerosis or rheumatoid arthritis susceptibility. J Rheumatol. 2011;38(3):446–9. Epub 2010 Dec 15.PubMedCrossRef Broen JC, Coenen MJ, Rueda B, Witte T, Padyukov L, Klareskog L, Hesselstrand R, Wuttge DM, Simeon C, Ortego-Centeno N, González-Gay MA, Pros A, Hunzelman N, Riemekasten G, Kreuter A, Vonk M, Scorza R, Beretta L, Airò P, van Riel PL, Kimberly R, Martin J, Edberg J, Radstake TR. The functional polymorphism 844 A>G in FcαRI (CD89) does not contribute to systemic sclerosis or rheumatoid arthritis susceptibility. J Rheumatol. 2011;38(3):446–9. Epub 2010 Dec 15.PubMedCrossRef

go back to reference Wipff J, Bonnet P, Ruiz B, Dieude P, Avouac J, Tiev K, Hachulla E, Cracowski JL, Diot E, Sibilia J, Mouthon L, Meyer O, Kahan A, Boileau C, Allanore Y. Association study of serotonin transporter gene (SLC6A4) in systemic sclerosis in European Caucasian populations. J Rheumatol. 2010;37(6):1164–7. Epub 2010 Apr 15.PubMedCrossRef Wipff J, Bonnet P, Ruiz B, Dieude P, Avouac J, Tiev K, Hachulla E, Cracowski JL, Diot E, Sibilia J, Mouthon L, Meyer O, Kahan A, Boileau C, Allanore Y. Association study of serotonin transporter gene (SLC6A4) in systemic sclerosis in European Caucasian populations. J Rheumatol. 2010;37(6):1164–7. Epub 2010 Apr 15.PubMedCrossRef

go back to reference Wipff J, Dieude P, Avouac J, Tiev K, Hachulla E, Cracowski JL, Diot E, Sibilia J, Mouthon L, Meyer O, Kahan A, Boileau C, Allanore Y. Association of metalloproteinase gene polymorphisms with systemic sclerosis in the European Caucasian population. J Rheumatol. 2010;37(3):599–602. Epub 2010 Jan 28.PubMedCrossRef Wipff J, Dieude P, Avouac J, Tiev K, Hachulla E, Cracowski JL, Diot E, Sibilia J, Mouthon L, Meyer O, Kahan A, Boileau C, Allanore Y. Association of metalloproteinase gene polymorphisms with systemic sclerosis in the European Caucasian population. J Rheumatol. 2010;37(3):599–602. Epub 2010 Jan 28.PubMedCrossRef

go back to reference Zhou X, Tan FK, Wang N, Xiong M, Maghidman S, Reveille JD, Milewicz DM, Chakraborty R, Arnett FC. Genome-wide association study for regions of systemic sclerosis susceptibility in a Choctaw Indian population with high disease prevalence. Arthritis Rheum. 2003;48(9):2585–92.PubMedCrossRef Zhou X, Tan FK, Wang N, Xiong M, Maghidman S, Reveille JD, Milewicz DM, Chakraborty R, Arnett FC. Genome-wide association study for regions of systemic sclerosis susceptibility in a Choctaw Indian population with high disease prevalence. Arthritis Rheum. 2003;48(9):2585–92.PubMedCrossRef

go back to reference Zhou X, Lee JE, Arnett FC, Xiong M, Park MY, Yoo YK, Shin ES, Reveille JD, Mayes MD, Kim JH, Song R, Choi JY, Park JA, Lee YJ, Lee EY, Song YW, Lee EB. HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans. Arthritis Rheum. 2009;60(12):3807–14.PubMedCrossRef Zhou X, Lee JE, Arnett FC, Xiong M, Park MY, Yoo YK, Shin ES, Reveille JD, Mayes MD, Kim JH, Song R, Choi JY, Park JA, Lee YJ, Lee EY, Song YW, Lee EB. HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans. Arthritis Rheum. 2009;60(12):3807–14.PubMedCrossRef

go back to reference • Radstake TR, Gorlova O, Rueda B, Martin JE, Alizadeh BZ, Palomino-Morales R, Coenen MJ, Vonk MC, Voskuyl AE, Schuerwegh AJ, Broen JC, van Riel PL, van 't Slot R, Italiaander A, Ophoff RA, Riemekasten G, Hunzelmann N, Simeon CP, Ortego-Centeno N, González-Gay MA, González-Escribano MF; Spanish Scleroderma Group, Airo P, van Laar J, Herrick A, Worthington J, Hesselstrand R, Smith V, de Keyser F, Houssiau F, Chee MM, Madhok R, Shiels P, Westhovens R, Kreuter A, Kiener H, de Baere E, Witte T, Padykov L, Klareskog L, Beretta L, Scorza R, Lie BA, Hoffmann-Vold AM, Carreira P, Varga J, Hinchcliff M, Gregersen PK, Lee AT, Ying J, Han Y, Weng SF, Amos CI, Wigley FM, Hummers L, Nelson JL, Agarwal SK, Assassi S, Gourh P, Tan FK, Koeleman BP, Arnett FC, Martin J, Mayes MD. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet. 2010 May;42(5):426–9. Epub 2010 Apr 11. This study is of particular importance because it investigated the genetic susceptibility to SSc in a non–hypothesis-driven way, further substantiating a common genetic background for AIDs. • Radstake TR, Gorlova O, Rueda B, Martin JE, Alizadeh BZ, Palomino-Morales R, Coenen MJ, Vonk MC, Voskuyl AE, Schuerwegh AJ, Broen JC, van Riel PL, van 't Slot R, Italiaander A, Ophoff RA, Riemekasten G, Hunzelmann N, Simeon CP, Ortego-Centeno N, González-Gay MA, González-Escribano MF; Spanish Scleroderma Group, Airo P, van Laar J, Herrick A, Worthington J, Hesselstrand R, Smith V, de Keyser F, Houssiau F, Chee MM, Madhok R, Shiels P, Westhovens R, Kreuter A, Kiener H, de Baere E, Witte T, Padykov L, Klareskog L, Beretta L, Scorza R, Lie BA, Hoffmann-Vold AM, Carreira P, Varga J, Hinchcliff M, Gregersen PK, Lee AT, Ying J, Han Y, Weng SF, Amos CI, Wigley FM, Hummers L, Nelson JL, Agarwal SK, Assassi S, Gourh P, Tan FK, Koeleman BP, Arnett FC, Martin J, Mayes MD. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet. 2010 May;42(5):426–9. Epub 2010 Apr 11. This study is of particular importance because it investigated the genetic susceptibility to SSc in a non–hypothesis-driven way, further substantiating a common genetic background for AIDs.

go back to reference Gorman CL, Russell AI, Zhang Z, Cunninghame Graham D, Cope AP, Vyse TJ. Polymorphisms in the CD3Z gene influence TCRzeta expression in systemic lupus erythematosus patients and healthy controls. J Immunol. 2008;180(2):1060–70.PubMed Gorman CL, Russell AI, Zhang Z, Cunninghame Graham D, Cope AP, Vyse TJ. Polymorphisms in the CD3Z gene influence TCRzeta expression in systemic lupus erythematosus patients and healthy controls. J Immunol. 2008;180(2):1060–70.PubMed

go back to reference Dieudé P, Boileau C, Guedj M, Avouac J, Ruiz B, Hachulla E, Diot E, Cracowski JL, Tiev K, Sibilia J, Mouthon L, Frances C, Amoura Z, Carpentier P, Cosnes A, Meyer O, Kahan A, Chiocchia G, Allanore Y. Independent replication establishes the CD247 gene as a genetic systemic sclerosis susceptibility factor. Ann Rheum Dis. 2011 Apr 7. [Epub ahead of print]. Dieudé P, Boileau C, Guedj M, Avouac J, Ruiz B, Hachulla E, Diot E, Cracowski JL, Tiev K, Sibilia J, Mouthon L, Frances C, Amoura Z, Carpentier P, Cosnes A, Meyer O, Kahan A, Chiocchia G, Allanore Y. Independent replication establishes the CD247 gene as a genetic systemic sclerosis susceptibility factor. Ann Rheum Dis. 2011 Apr 7. [Epub ahead of print].

go back to reference • Gorlova O, Martin JE, Rueda B, Koeleman BPC, Ying J, Teruel M, Diaz-Gallo LM, Broen J, Vonk MC, Simeon CP, Alizadeh BZ, Coenen MJH, Voskuyl AE, Schuerwegh AJ, Van Riel PLCM, Vanthuyne M, Van‘t Slot R, Italiaander, Ophoff RA, Hunzelmann N, Fonollosa V, Ortego-Centeno N, González-Gay MA, García-Hernández FJ, González-Escribano MF, Airo’ P, Van Laar J, Worthington J, Hesselstrand R, Smith V, De Keyser F, Houssiau F, Chee MM, Madhok R, Shiels P, Westhovens R, Kreuter A, De Baere E, Witte T, Padyukov L, Nordin A, Scorza R, Lunardi C, Lie BA, Hoffmann-Vold AM, De la Peña PG, Carreira P, Varga J, Hinchcliff M, Lee AT, Gourh P, Amos CI, Wigley FM, Hummers LK, Nelson JL, Riemekasten G, Herrick A, Beretta L, Fonseca C, Denton CP, Gregersen PK, Agarwal S, Assassi S, Tan FK, Arnett FC, Radstake TRDJ, Mayes MD, Martin J. Identification of novel genetic markers associated with clinical phenotypes and autoantibody subsets of systemic sclerosis through a genome wide association strategy. PLoS Genet. 2011. This study is of particular interest because it indicates that the heterogeneity of SSc phenotypes is likely to be the reflection of a different genetic foundation. • Gorlova O, Martin JE, Rueda B, Koeleman BPC, Ying J, Teruel M, Diaz-Gallo LM, Broen J, Vonk MC, Simeon CP, Alizadeh BZ, Coenen MJH, Voskuyl AE, Schuerwegh AJ, Van Riel PLCM, Vanthuyne M, Van‘t Slot R, Italiaander, Ophoff RA, Hunzelmann N, Fonollosa V, Ortego-Centeno N, González-Gay MA, García-Hernández FJ, González-Escribano MF, Airo’ P, Van Laar J, Worthington J, Hesselstrand R, Smith V, De Keyser F, Houssiau F, Chee MM, Madhok R, Shiels P, Westhovens R, Kreuter A, De Baere E, Witte T, Padyukov L, Nordin A, Scorza R, Lunardi C, Lie BA, Hoffmann-Vold AM, De la Peña PG, Carreira P, Varga J, Hinchcliff M, Lee AT, Gourh P, Amos CI, Wigley FM, Hummers LK, Nelson JL, Riemekasten G, Herrick A, Beretta L, Fonseca C, Denton CP, Gregersen PK, Agarwal S, Assassi S, Tan FK, Arnett FC, Radstake TRDJ, Mayes MD, Martin J. Identification of novel genetic markers associated with clinical phenotypes and autoantibody subsets of systemic sclerosis through a genome wide association strategy. PLoS Genet. 2011. This study is of particular interest because it indicates that the heterogeneity of SSc phenotypes is likely to be the reflection of a different genetic foundation.

go back to reference Allanore Y, Saad M, Dieudé, Avouac J, Distler JHW, Amouye P, Matucci-Cerinic M, Riemekasten G, Airo’ P, Melchers I, Hachulla E, Daniele C, Wichmann HE, Wipff J, Lambert JC, Hunzelmann N, Tiev K, Caramaschi P, Diot E, Kowal-Bielecka O, Valentini G, Mouthon L, Czirják L, Damjanov N, Salvi E, Conti C, Muller M, Muller-Ladner U, Riccieri V, Ruiz B, Cracowski JL, Letenneur L, Dupuy AM, Meyer O, Kahan A, Munnich A, Boileau C, Martinez M. Genomewide scan identifies TNIP1, PSORS1C1 and RHOB as novel risk loci for Systemic Sclerosis. PLoS Genet. 2011. Allanore Y, Saad M, Dieudé, Avouac J, Distler JHW, Amouye P, Matucci-Cerinic M, Riemekasten G, Airo’ P, Melchers I, Hachulla E, Daniele C, Wichmann HE, Wipff J, Lambert JC, Hunzelmann N, Tiev K, Caramaschi P, Diot E, Kowal-Bielecka O, Valentini G, Mouthon L, Czirják L, Damjanov N, Salvi E, Conti C, Muller M, Muller-Ladner U, Riccieri V, Ruiz B, Cracowski JL, Letenneur L, Dupuy AM, Meyer O, Kahan A, Munnich A, Boileau C, Martinez M. Genomewide scan identifies TNIP1, PSORS1C1 and RHOB as novel risk loci for Systemic Sclerosis. PLoS Genet. 2011.

go back to reference Dieudé P, Wipff J, Guedj M, Ruiz B, Melchers I, Hachulla E, Riemekasten G, Diot E, Hunzelmann N, Sibilia J, Tiev K, Mouthon L, Cracowski JL, Carpentier PH, Distler J, Amoura Z, Tarner I, Avouac J, Meyer O, Kahan A, Boileau C, Allanore Y. BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4. Arthritis Rheum. 2009;60(11):3447–54.PubMedCrossRef Dieudé P, Wipff J, Guedj M, Ruiz B, Melchers I, Hachulla E, Riemekasten G, Diot E, Hunzelmann N, Sibilia J, Tiev K, Mouthon L, Cracowski JL, Carpentier PH, Distler J, Amoura Z, Tarner I, Avouac J, Meyer O, Kahan A, Boileau C, Allanore Y. BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4. Arthritis Rheum. 2009;60(11):3447–54.PubMedCrossRef

go back to reference Coustet B, Dieudé P, Guedj M, Bouaziz M, Avouac J, Ruiz B, Hachulla E, Diot E, Kracowski JL, Tiev K, Sibilia J, Mouthon L, Frances C, Amoura Z, Carpentier P, Cosnes A, Meyer O, Kahan A, Boileau C, Chiocchia G, Allanore Y. C8orf 13/BLK is a genetic risk locus for systemic sclerosis and has additive effect with BANK1: results from a large French cohort and meta-analysis. Arthritis Rheum. 2011. doi:10.1002/art.30379 [Epub ahead of print]. Coustet B, Dieudé P, Guedj M, Bouaziz M, Avouac J, Ruiz B, Hachulla E, Diot E, Kracowski JL, Tiev K, Sibilia J, Mouthon L, Frances C, Amoura Z, Carpentier P, Cosnes A, Meyer O, Kahan A, Boileau C, Chiocchia G, Allanore Y. C8orf 13/BLK is a genetic risk locus for systemic sclerosis and has additive effect with BANK1: results from a large French cohort and meta-analysis. Arthritis Rheum. 2011. doi:10.​1002/​art.​30379 [Epub ahead of print].

go back to reference • Beretta L, Santaniello A, Mayo M, Cappiello F, Marchini M, Scorza R. A 3-factor epistatic model predicts digital ulcers in Italian scleroderma patients. Eur J Intern Med. 2010 Aug;21(4):347–53. Epub 2010 Jun 23. This study may be a prelude to a method investigating the additive effects of multiple polymorphisms on SSc complication development; it also shows that these genetic models do not necessarily need to consist of previously associated genes. • Beretta L, Santaniello A, Mayo M, Cappiello F, Marchini M, Scorza R. A 3-factor epistatic model predicts digital ulcers in Italian scleroderma patients. Eur J Intern Med. 2010 Aug;21(4):347–53. Epub 2010 Jun 23. This study may be a prelude to a method investigating the additive effects of multiple polymorphisms on SSc complication development; it also shows that these genetic models do not necessarily need to consist of previously associated genes.