IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms
Abstract
:1. Introduction
2. Materials and Methodology
2.1. Study Population
2.2. Selection of Single-Nucleotide Polymorphisms and Genotyping Method
2.3. Statistical Analysis
3. Results
3.1. CD40, BLK and BANK1 Genotype and Allele Frequencies in Patients with IgAV and Healthy Controls
3.2. CD40, BLK and BANK1 Genotype and Allele Frequencies in Patients with IgAV Stratified according to Specific Clinical Characteristics of the Disease
3.3. CD40, BLK and BANK1 Haplotype Analyses
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Shapiro-Shelef, M.; Calame, K. Regulation of plasma-cell development. Nat. Rev. Immunol. 2005, 5, 2302–2342. [Google Scholar] [CrossRef] [PubMed]
- Quezada, S.A.; Jarvinen, L.Z.; Lind, E.F.; Noelle, R.J. CD40/CD154 interactions at the interface of tolerance and immunity. Annu. Rev. Immunol. 2004, 22, 307–328. [Google Scholar] [CrossRef] [PubMed]
- Aiba, Y.; Yamazaki, T.; Okada, T.; Gotoh, K.; Sanjo, H.; Ogata, M.; Kurosaki, T. BANK Negatively Regulates Akt Activation and Subsequent B Cell Responses. Immunity 2006, 24, 259–268. [Google Scholar] [CrossRef] [PubMed]
- Suthers, A.N.; Sarantopoulos, S. TLR7/TLR9- and B Cell Receptor-Signaling Crosstalk: Promotion of Potentially Dangerous B Cells. Front. Immunol. 2017, 8, 775. [Google Scholar] [CrossRef] [PubMed]
- Dymecki, S.M.; Niederhuber, J.E.; Desiderio, S.V. Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells. Science 1990, 247, 332–336. [Google Scholar] [CrossRef] [PubMed]
- Tretter, T.; Ross, A.E.; Dordai, D.I.; Desiderio, S. Mimicry of pre-B cell receptor signaling by activation of the tyrosine kinase Blk. J. Exp. Med. 2003, 198, 1863–1873. [Google Scholar] [CrossRef] [PubMed]
- Castillejo-López, C.; Delgado-Vega, A.M.; Wojcik, J.; Kozyrev, S.V.; Thavathiru, E.; Wu, Y.-Y.; Sánchez, E.; Pöllmann, D.; López-Egido, J.R.; Fineschi, S.; et al. Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK. Ann. Rheum. Dis. 2012, 71, 136–142. [Google Scholar] [CrossRef]
- Kozyrev, S.V.; Abelson, A.-K.; Wojcik, J.; Zaghlool, A.; PrasadLinga, R.M.V.; Sanchez, E.; Gunnarsson, I.; Svenungsson, E.; Sturfelt, G.; Jönsen, A.; et al. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat. Genet. 2008, 40, 211–216. [Google Scholar] [CrossRef]
- García-Bermúdez, M.; González-Juanatey, C.; López-Mejías, R.; Teruel, M.; Corrales, A.; Miranda-Filloy, J.A.; Castañeda, S.; Balsa, A.; Fernández-Gutierrez, B.; González-Álvaro, I.; et al. Study of association of CD40-CD154 gene polymorphisms with disease susceptibility and cardiovascular risk in Spanish rheumatoid arthritis patients. PLoS ONE 2012, 7, e49214. [Google Scholar] [CrossRef]
- Jacobson, E.M.; Huber, A.K.; Akeno, N.; Sivak, M.; Li, C.W.; Concepcion, E.; Ho, K.; Tomer, Y. A CD40 Kozak sequence polymorphism and susceptibility to antibody-mediated autoimmune conditions: The role of CD40 tissue-specific expression. Genes Immun. 2007, 8, 205–214. [Google Scholar] [CrossRef] [Green Version]
- Kelly, F.; Matesanz, F.; Alcina, A.; Teruel, M.; Díaz-Gallo, L.M.; Gómez-García, M.; López-Nevot, M.A.; Rodrigo, L.; Nieto, A.; Cardeña, C.; et al. CD40: Novel association with Crohn’s disease and replication in multiple sclerosis susceptibility. PLoS ONE 2010, 5, e11520. [Google Scholar]
- Bahlo, M.; Booth, D.R.; Broadley, S.A.; Brown, M.A.; Foote, S.J.; Griffiths, L.R.; Kilpatrick, T.J.; Lechner-Scott, J.; Moscato, P.; Perreau, V.M.; et al. Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat. Genet. 2009, 41, 824–828. [Google Scholar]
- Onouchi, Y.; Ozaki, K.; Burns, J.C.; Shimizu, C.; Terai, M.; Hamada, H.; Honda, T.; Suzuki, H.; Suenaga, T.; Takeuchi, T.; et al. A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat. Genet. 2012, 44, 517–521. [Google Scholar] [CrossRef]
- Yang, W.; Shen, N.; Ye, D.-Q.; Liu, Q.; Zhang, Y.; Qian, X.-X.; Hirankarn, N.; Ying, D.; Pan, H.F.; Mok, C.C.; et al. Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genet. 2010, 6, e1000841. [Google Scholar] [CrossRef]
- Gregersen, P.K.; Amos, C.I.; Lee, A.T.; Lu, Y.; Remmers, E.F.; Kastner, D.L.; Seldin, M.F.; Criswell, L.A.; Plenge, R.M.; Holers, V.M.; et al. REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. Nat. Genet. 2009, 41, 820–823. [Google Scholar] [CrossRef]
- Gourh, P.; Agarwal, S.K.; Martin, E.; Divecha, D.; Rueda, B.; Bunting, H.; Assassi, S.; Paz, G.; Shete, S.; McNearney, T.; et al. Association of the C8orf13-BLK region with systemic sclerosis in North-American and European populations. J. Autoimmun. 2010, 34, 155–162. [Google Scholar] [CrossRef]
- Graham, R.R.; Cotsapas, C.; Davies, L.; Hackett, R.; Lessard, C.J.; Leon, J.M.; Burtt, N.P.; Guiducci, C.; Parkin, M.; Gates, C.; et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat. Genet. 2008, 40, 1059–1061. [Google Scholar] [CrossRef]
- Ramírez-Bello, J.; Fragoso, J.M.; Alemán-Ávila, I.; Jiménez-Morales, S.; Campos-Parra, A.D.; Barbosa-Cobos, R.E.; Moreno, J. Association of BLK and BANK1 Polymorphisms and Interactions With Rheumatoid Arthritis in a Latin-American Population. Front. Genet. 2020, 11, 58. [Google Scholar] [CrossRef]
- Orozco, G.; Abelson, A.-K.; González-Gay, M.A.; Balsa, A.; Pascual-Salcedo, D.; García, A.; Fernández-Gutierrez, B.; Petersson, I.; Pons-Estel, B.; Eimon, A.; et al. Study of functional variants of the BANK1 gene in rheumatoid arthritis. Arthritis Rheum. Off. J. Am. Coll. Rheumatol. 2009, 60, 372–379. [Google Scholar] [CrossRef]
- Rodríguez-Rodríguez, L.; Castañeda, S.; Vázquez-Rodríguez, T.R.; Morado, I.C.; Marí-Alfonso, B.; Gómez-Vaquero, C.; Miranda-Filloy, J.A.; Narvaez, J.; Ortego-Centeno, N.; Blanco, R.; et al. Influence of CD40 rs1883832 polymorphism in susceptibility to and clinical manifestations of biopsy-proven giant cell arteritis. J. Rheumatol. 2010, 37, 2076–2080. [Google Scholar] [CrossRef]
- Torres, O.; Palomino-Morales, R.; Vazquez-Rodriguez, T.R.; Castañeda, S.; Morado, I.C.; Miranda-Filloy, J.A.; Ortego-Centeno, N.; Fernandez-Gutierrez, B.; Martin, J.; Gonzalez-Gay, M.A. Role of the C8orf13-BLK region in biopsy-proven giant cell arteritis. Hum. Immunol. 2010, 71, 525–529. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.C.; Kuo, H.-C.; Chang, J.-S.; Chang, L.-Y.; Huang, L.-M.; Chen, M.-R.; Liang, C.-D.; Chi, H.; Huang, F.-Y.; Lee, M.-L.; et al. Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. Nat. Genet. 2012, 44, 522–525. [Google Scholar] [CrossRef] [PubMed]
- González-Gay, M.A.; García-Porrúa, C. Epidemiology of the vasculitides. Rheum. Dis. Clin. N. Am. 2001, 27, 729–749. [Google Scholar] [CrossRef]
- Calviño, M.C.; Llorca, J.; García-Porrúa, C.; Fernández-Iglesias, J.L.; Rodriguez-Ledo, P.; González-Gay, M.A. Henoch-Schönlein purpura in children from northwestern Spain: A 20-year epidemiologic and clinical study. Medicine 2001, 80, 279–290. [Google Scholar] [CrossRef]
- García-Porrúa, C.; Calviño, M.C.; Llorca, J.; Couselo, J.M.; González-Gay, M.A. Henoch-Schönlein purpura in children and adults: Clinical differences in a defined population. Semin. Arthritis Rheum. 2002, 32, 149–156. [Google Scholar] [CrossRef]
- Calvo-Río, V.; Loricera, J.; Mata, C.; Martín, L.; Ortiz-Sanjuán, F.; Alvarez, L.; González-Vela, M.C.; González-Lamuño, D.; Rueda-Gotor, J.; Fernández-Llaca, H.; et al. Henoch-Schönlein purpura in northern Spain: Clinical spectrum of the disease in 417 patients from a single center. Medicine 2014, 93, 106–113. [Google Scholar] [CrossRef]
- González-Gay, M.A.; Blanco, R.; Castañeda, S. Henoch-Schönlein purpura (IgA vasculitis): The paradox of the different incidence and clinical spectrum in children and adults. Clin. Exp. Rheumatol. 2017, 35 (Suppl. S103), 3–4. [Google Scholar]
- González-Gay, M.A.; García-Porrúa, C. Systemic vasculitis in adults in Northwestern Spain, 1988–1997: Clinical and epidemiologic aspects. Medicine 1999, 78, 292–308. [Google Scholar] [CrossRef]
- Calvo-Río, V.; Hernández, J.L.; Ortiz-Sanjuán, F.; Loricera, J.; Palmou-Fontana, N.; González-Vela, M.C.; González-Lamuño, D.; González-López, M.A.; Armesto, S.; Blanco, R.; et al. Relapses in patients with Henoch-Schönlein purpura: Analysis of 417 patients from a single center. Medicine 2016, 95, e4217. [Google Scholar] [CrossRef]
- López-Mejías, R.; Castañeda, S.; Genre, F.; Remuzgo-Martínez, S.; Carmona, F.D.; Llorca, J.; Blanco, R.; Martín, J.; González-Gay, M.A. Genetics of immunoglobulin-A vasculitis (Henoch-Schönlein purpura): An updated review. Autoimmun. Rev. 2018, 17, 301–315. [Google Scholar] [CrossRef]
- López-Mejías, R.; Genre, F.; Pérez, B.S.; Castañeda, S.; Ortego-Centeno, N.; Llorca, J.; Ubilla, B.; Remuzgo-Martínez, S.; Mijares, V.; Pina, T.; et al. HLA-DRB1 association with Henoch-Schonlein purpura. Arthritis Rheumatol. 2015, 67, 823–827. [Google Scholar] [CrossRef]
- López-Mejías, R.; Genre, F.; Pérez, B.S.; Castañeda, S.; Ortego-Centeno, N.; Llorca, J.; Ubilla, B.; Remuzgo-Martínez, S.; Mijares, V.; Pina, T.; et al. Association of HLA-B*41:02 with Henoch-Schönlein Purpura (IgA Vasculitis) in Spanish individuals irrespective of the HLA-DRB1 status. Arthritis Res. Ther. 2015, 17, 102. [Google Scholar] [CrossRef]
- Michel, B.A.; Hunder, G.G.; Bloch, D.A.; Calabrese, L.H. Hypersensitivity vasculitis and Henoch-Schönlein purpura: A comparison between the 2 disorders. J. Rheumatol. 1992, 19, 721–728. [Google Scholar]
- Mills, J.A.; Michel, B.A.; Bloch, D.A.; Calabrese, L.H.; Hunder, G.G.; Arend, W.P.; Edworthy, S.M.; Fauci, A.S.; Leavitt, R.Y.; Lie, J.T.; et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura. Arthritis Rheum. 1990, 33, 1114–1121. [Google Scholar] [CrossRef]
- Jennette, J.C.; Falk, R.J.; Bacon, P.A.; Basu, N.; Cid, M.C.; Ferrario, F.; Flores-Suarez, L.F.; Gross, W.L.; Guillevin, L.; Hagen, E.C.; et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013, 65, 1–11. [Google Scholar] [CrossRef]
- Hom, G.; Graham, R.R.; Modrek, B.; Taylor, K.E.; Ortmann, W.; Garnier, S.; Lee, A.T.; Chung, S.S.; Ferreira, R.C.; Krishna Pant, P.V.; et al. Association of systemic lupus erythematosus with C8orf13–BLK and ITGAM–ITGAX. Engl. J. Med. 2008, 358, 900–909. [Google Scholar]
- Lipsky, P.E. Systemic lupus erythematosus: An autoimmune disease of B cell hyperactivity. Nat. Immunol. 2001, 2, 764–766. [Google Scholar] [CrossRef]
- Yanaba, K.; Bouaziz, J.-D.; Matsushita, T.; Magro, C.M.; William St Clair, E.; Tedder, T.F. B-lymphocyte contributions to human autoimmune disease. Immunol. Rev. 2008, 223, 284–299. [Google Scholar] [CrossRef]
- López-Mejías, R.; Genre, F.; Remuzgo-Martínez, S.; Sevilla Pérez, B.; Castañeda, S.; Llorca, J.; Ortego-Centeno, N.; Ubilla, B.; Mijares, V.; Pina, T.; et al. Interleukin 1 beta (IL1ß) rs16944 genetic variant as a genetic marker of severe renal manifestations and renal sequelae in Henoch-Schönlein purpura. Clin. Exp. Rheumatol. 2016, 34 (Suppl. S97), S84–S88. [Google Scholar]
- Amoli, M.M.; Thomson, W.; Hajeer, A.H.; Calviño, M.C.; Garcia-Porrua, C.; Ollier, W.E.R.; Gonzalez-Gay, M.A. Interleukin 1 receptor antagonist gene polymorphism is associated with severe renal involvement and renal sequelae in Henoch-Schönlein purpura. J. Rheumatol. 2002, 29, 1404–1407. [Google Scholar]
- Amoli, M.M.; Thomson, W.; Hajeer, A.H.; Calviño, M.C.; Garcia-Porrua, C.; Ollier, W.E.R.; Gonzalez-Gay, M.A. Interleukin 8 gene polymorphism is associated with increased risk of nephritis in cutaneous vasculitis. J. Rheumatol. 2002, 29, 2367–2370. [Google Scholar]
- Amoli, M.M.; Mattey, D.L.; Calviño, M.C.; Garcia-Porrua, C.; Thomson, W.; Hajeer, A.H. Polymorphism at codon 469 of the intercellular adhesion molecule-1 locus is associated with protection against severe gastrointestinal complications in Henoch-Schönlein purpura. J. Rheumatol. 2001, 28, 1014–1018. [Google Scholar]
- Carmona, E.G.; García-Giménez, J.A.; López-Mejías, R.; Chuen Khor, C.; Lee, J.-K.; Taskiran, E.; Ozen, S.; Hocevar, A.; Liu, L.; Gorenjak, M.; et al. Identification of a shared genetic risk locus for Kawasaki disease and immunoglobulin A vasculitis by a cross-phenotype meta-analysis. Rheumatology 2022, 61, 1204–1210. [Google Scholar] [CrossRef]
- Ortiz-Fernández, L.; Carmona, F.D.; López-Mejías, R.; González-Escribano, M.F.; Lyons, P.A.; Morgan, A.W.; Sawalha, A.H.; Merkel, P.A.; Smith, K.G.C.; González-Gay, M.A.; et al. Cross-phenotype analysis of Immunochip data identifies KDM4C as a relevant locus for the development of systemic vasculitis. Ann. Rheum. Dis. 2018, 77, 589–595. [Google Scholar] [CrossRef] [PubMed]
- Torres, O.; Palomino-Morales, R.; Castañeda, S.; Vazquez-Rodriguez, T.R.; Morado, I.C.; Miranda-Filloy, J.A.; Amigo-Diaz, E.; Vicente, E.F.; Ortego-Centeno, N.; Fernandez-Gutierrez, B.; et al. Role of BANK1 gene polymorphisms in biopsy-proven giant cell arteritis. J. Rheumatol. 2010, 37, 1502–1504. [Google Scholar] [CrossRef] [PubMed]
- Montúfar-Robles, I.; Soto, M.E.; Jiménez-Morales, S.; Gamboa, R.; Huesca-Gómez, C.; Ramírez-Bello, J. Polymorphisms in TNFAIP3, but not in STAT4, BANK1, BLK, and TNFSF4, are associated with susceptibility to Takayasu arteritis. Cell. Immunol. 2021, 365, 104375. [Google Scholar] [CrossRef] [PubMed]
- Donadio, J.V.; Grande, J.P. IgA nephropathy. N. Engl. J. Med. 2002, 347, 738–748. [Google Scholar] [CrossRef]
- Wyatt, R.J.; Julian, B.A. IgA nephropathy. N. Engl. J. Med. 2013, 368, 2402–2414. [Google Scholar] [CrossRef]
- Gharavi, A.G.; Kiryluk, K.; Choi, M.; Li, Y.; Hou, P.; Xie, J.; Sanna-Cherchi, S.; Men, C.J.; Julian, B.A.; Wyatt, R.J.; et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat. Genet. 2011, 43, 321–327. [Google Scholar] [CrossRef]
- Yu, X.-Q.; Li, M.; Zhang, H.; Low, H.-Q.; Wei, X.; Wang, J.-Q.; Sun, L.-D.; Sim, K.-S.; Li, Y.; Foo, J.-N.; et al. A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nat. Genet. 2011, 44, 178–182. [Google Scholar] [CrossRef]
- Kiryluk, K.; Li, Y.; Scolari, F.; Panacherie, S.; Choi, M.; Verbitsky, M.; Fasel, D.; Lata, S.; Prakash, S.; Shapiro, S.; et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat. Genet. 2014, 46, 1187–1196. [Google Scholar] [CrossRef] [Green Version]
% (n) | |
---|---|
Children (age ≤20 years)/adults (age >20 years) (n) | 296/86 |
Percentage of females | 47.4 |
Age at disease onset (years, median [IQR]) | 7 [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19] |
Duration of follow up (years, median [IQR]) | 1 [1,2,3] |
Palpable purpura and/or maculopapular rash | 100 (382) |
Arthralgia and/or arthritis | 55.5 (212) |
GI manifestations (if “a” and/or “b”) | 53.1 (203) |
(a) Bowel angina | 50.3 (192) |
(b) GI bleeding | 16.8 (64) |
Renal manifestations (if any of the following characteristics) | 36.1 (138) |
(a) Hematuria 1 | 34.8 (133) |
(b) Proteinuria 1 | 33.5 (128) |
(c) Nephrotic syndrome 1 | 5.8 (22) |
(d) Renal sequelae (persistent renal involvement) 2 | 6.8 (26) |
Change | Genotypes, % (n) | Allele Test1 | ||||||
---|---|---|---|---|---|---|---|---|
Locus | SNP | 1/2 | Sample Set | 1/1 | 1/2 | 2/2 | p | OR [95% CI] |
CD40 | rs1883832 | C/T | IgAV patients | 54.0 (205) | 36.8 (140) | 9.2 (35) | 0.69 | 1.04 [0.86–1.26] |
Healthy controls | 53.1 (507) | 40.1 (383) | 6.8 (65) | |||||
rs1535045 | C/T | IgAV patients | 53.6 (201) | 39.5 (148) | 6.9 (26) | 0.45 | 1.08 [0.88–1.31] | |
Healthy controls | 56.8 (542) | 36.0 (344) | 7.2 (69) | |||||
rs4813003 | C/T | IgAV patients | 77.9 (292) | 20.0 (75) | 2.1 (8) | 0.35 | 0.88 [0.68–1.15] | |
Healthy controls | 75.5 (721) | 22.0 (210) | 2.5 (24) | |||||
BLK | rs2254546 | G/A | IgAV patients | 74.1 (278) | 22.4 (84) | 3.5 (13) | 0.74 | 0.96 [0.75–1.22] |
Healthy controls | 71.5 (683) | 26.6 (254) | 1.9 (18) | |||||
rs2736340 | C/T | IgAV patients | 63.0 (238) | 31.7 (120) | 5.3 (20) | 0.60 | 0.95 [0.77–1.17] | |
Healthy controls | 60.0 (573) | 35.8 (342) | 4.2 (40) | |||||
rs2618476 | T/C | IgAV patients | 60.2 (228) | 34.3 (130) | 5.5 (21) | 0.69 | 0.96 [0.78–1.18] | |
Healthy controls | 57.9 (553) | 37.4 (357) | 4.7 (45) | |||||
BANK1 | rs10516487 | G/A | IgAV patients | 52.5 (200) | 40.2 (153) | 7.3 (28) | 0.80 | 0.98 [0.81–1.18] |
Healthy controls | 51.2 (489) | 41.8 (399) | 7.0 (67) | |||||
rs3733197 | G/A | IgAV patients | 50.0 (188) | 39.1 (147) | 10.9 (41) | 0.53 | 1.06 [0.88–1.28] | |
Healthy controls | 50.0 (478) | 41.5 (396) | 8.5 (81) |
Locus | SNP | Children (Age ≤20 Years) | GI Manifestations 1 | Renal Manifestations 2 | |||
---|---|---|---|---|---|---|---|
Yes (n = 296) | No (n = 86) | Yes (n = 203) | No (n = 179) | Yes (n = 138) | No (n = 244) | ||
CD40 | rs1883832 | ||||||
CC | 53.7 (159) | 54.8 (46) | 52.2 (105) | 55.9 (100) | 54.4 (74) | 53.7 (131) | |
CT | 38.2 (113) | 32.1 (27) | 39.3 (79) | 34.1 (61) | 36.8 (50) | 36.9 (90) | |
TT | 8.1 (24) | 13.1 (11) | 8.5 (17) | 10.0 (18) | 8.8 (12) | 9.4 (23) | |
C | 72.8 (431) | 70.8 (119) | 71.9 (289) | 72.9 (261) | 72.8 (198) | 72.1 (352) | |
T | 27.2 (161) | 29.2 (49) | 28.1 (113) | 27.1 (97) | 27.2 (74) | 27.9 (136) | |
rs1535045 | |||||||
CC | 54.3 (158) | 51.2 (43) | 50.3 (100) | 57.4 (101) | 50.4 (68) | 55.4 (133) | |
CT | 38.1 (111) | 44.0 (37) | 42.2 (84) | 36.4 (64) | 41.5 (56) | 38.3 (92) | |
TT | 7.6 (22) | 4.8 (4) | 7.5 (15) | 6.2 (11) | 8.1 (11) | 6.3 (15) | |
C | 73.4 (427) | 73.2 (123) | 71.4 (284) | 75.6 (266) | 71.1 (192) | 74.6 (358) | |
T | 26.6 (155) | 26.8 (45) | 28.6 (114) | 24.4 (86) | 28.9 (78) | 25.4 (122) | |
rs4813003 | |||||||
CC | 77.0 (224) | 80.9 (68) | 75.2 (152) | 80.9 (140) | 81.7 (112) | 75.6 (180) | |
CT | 21.3 (62) | 15.5 (13) | 21.8 (44) | 17.9 (31) | 16.1 (22) | 22.3 (53) | |
TT | 1.7 (5) | 3.6 (3) | 3.0 (6) | 1.2 (2) | 2.2 (3) | 2.1 (5) | |
C | 87.6 (510) | 88.7 (149) | 86.1 (348) | 89.9 (311) | 89.8 (246) | 86.8 (413) | |
T | 12.4 (72) | 11.3 (19) | 13.9 (56) | 10.1 (35) | 10.2 (28) | 13.2 (63) | |
rs2254546 | |||||||
BLK | GG | 74.5 (216) | 73.0 (62) | 77.9 (155) | 69.9 (123) | 73.3 (99) | 74.6 (179) |
GA | 22.1 (64) | 23.5 (20) | 18.6 (37) | 26.7 (47) | 23.7 (32) | 21.7 (52) | |
AA | 3.4 (10) | 3.5 (3) | 3.5 (7) | 3.4 (6) | 3.0 (4) | 3.7 (9) | |
G | 85.5 (496) | 84.7 (144) | 87.2 (347) | 83.2 (293) | 85.2 (230) | 85.4 (410) | |
A | 14.5 (84) | 15.3 (26) | 12.8 (51) | 16.8 (59) | 14.8 (40) | 14.6 (70) | |
rs2736340 | |||||||
CC | 63.1 (185) | 62.4 (53) | 64.8 (129) | 60.9 (109) | 69.1 (94) | 59.5 (144) | |
CT | 31.4 (92) | 32.9 (28) | 30.2 (60) | 33.5 (60) | 27.2 (37) | 34.3 (83) | |
TT | 5.5 (16) | 4.7 (4) | 5.0 (10) | 5.6 (10) | 3.7 (5) | 6.2 (15) | |
C | 78.8 (462) | 78.8 (134) | 79.9 (318) | 77.7 (278) | 82.7 (225) | 76.7 (371) | |
T | 21.2 (124) | 21.2 (36) | 20.1 (80) | 22.3 (80) | 17.3 (47) | 23.3 (113) | |
rs2618476 | |||||||
TT | 60.2 (177) | 60.0 (51) | 61.9 (125) | 58.2 (103) | 65.0 (89) | 57.4 (139) | |
TC | 33.3 (98) | 37.6 (32) | 34.1 (69) | 34.5 (61) | 32.1 (44) | 35.6 (86) | |
CC | 6.5 (19) | 2.4 (2) | 4.0 (8) | 7.3 (13) | 2.9 (4) | 7.0 (17) | |
T | 76.9 (452) | 78.8 (134) | 79.0 (319) | 75.4 (267) | 81.0 (222) | 75.2 (364) | |
C | 23.1 (136) | 21.2 (36) | 21.0 (85) | 24.6 (87) | 19.0 (52) | 24.8 (120) | |
BANK1 | rs10516487 | ||||||
GG | 52.5 (155) | 52.3 (45) | 51.0 (103) | 54.2 (97) | 50.0 (69) | 53.9 (131) | |
GA | 40.0 (118) | 40.7 (35) | 41.1 (83) | 39.1 (70) | 40.6 (56) | 39.9 (97) | |
AA | 7.5 (22) | 7.0 (6) | 7.9 (16) | 6.7 (12) | 9.4 (13) | 6.2 (15) | |
G | 72.5 (428) | 72.7 (125) | 71.5 (289) | 73.7 (264) | 70.3 (194) | 73.9 (359) | |
A | 27.5 (162) | 27.3 (47) | 28.5 (115) | 26.3 (94) | 29.7 (82) | 26.1 (127) | |
rs3733197 | |||||||
GG | 48.6 (141) | 54.6 (47) | 47.5 (95) | 52.8 (93) | 46.0 (63) | 52.3 (125) | |
GA | 41.4 (120) | 31.4 (27) | 43.5 (87) | 34.1 (60) | 41.6 (57) | 37.7 (90) | |
AA | 10.0 (29) | 14.0 (12) | 9.0 (18) | 13.1 (23) | 12.4 (17) | 10.0 (24) | |
G | 69.3 (402) | 70.3 (121) | 69.2 (277) | 69.9 (246) | 66.8 (183) | 71.1 (340) | |
A | 30.7 (178) | 29.7 (51) | 30.8 (123) | 30.1 (106) | 33.2 (91) | 28.9 (138) |
CD40 | p | OR [95% CI] | ||
---|---|---|---|---|
rs1883832 | rs1535045 | rs4813003 | ||
C | C | C | - | Ref. |
C | T | C | 0.78 | 0.97 [0.76–1.23] |
T | C | C | 0.22 | 0.85 [0.65–1.11] |
T | C | T | 0.22 | 1.24 [0.87–1.81] |
BLK | p | OR [95% CI] | ||
rs2254546 | rs2736340 | rs2618476 | ||
G | C | T | - | Ref. |
G | T | C | 0.10 | 1.22 [0.96–1.56] |
A | C | T | 0.05 | 1.35 [0.99–1.86] |
A | T | C | 0.44 | 0.85 [0.55–1.33] |
BANK1 | p | OR [95% CI] | ||
rs10516487 | rs3733197 | |||
G | G | - | Ref. | |
A | A | 0.90 | 1.01 [0.82–1.26] | |
G | A | 0.06 | 0.74 [0.53–1.03] | |
A | G | 0.66 | 0.92 [0.62–1.38] |
Age of Onset | Presence/Absence of GI Manifestations 1 | Presence/Absence of Renal Manifestations 2 | ||||||
---|---|---|---|---|---|---|---|---|
CD40 | p | OR [95% CI] | p | OR [95% CI] | p | OR [95% CI] | ||
rs1883832 | rs1535045 | rs4813003 | ||||||
C | C | C | - | Ref. | - | Ref. | - | Ref. |
C | T | C | 0.64 | 0.89 [0.55–1.48] | 0.14 | 1.34 [0.89–2.04] | 0.12 | 1.37 [0.90–2.09] |
T | C | C | 0.26 | 1.34 [0.78–2.35] | 0.84 | 1.04 [0.66–1.65] | 0.25 | 1.30 [0.81–2.06] |
T | C | T | 0.17 | 0.63 [0.31–1.34] | 0.46 | 1.26 [0.65–2.47] | 0.15 | 0.60 [0.26–1.25] |
BLK | p | OR [95% CI] | p | OR [95% CI] | p | OR [95% CI] | ||
rs2254546 | rs2736340 | rs2618476 | ||||||
G | C | T | - | Ref. | - | Ref. | - | Ref. |
G | T | C | 0.31 | 1.30 [0.77–2.27] | 0.73 | 0.93 [0.61–1.43] | 0.07 | 0.66 [0.41–1.05] |
A | C | T | 0.41 | 1.32 [0.67–2.81] | 0.44 | 0.81 [0.46–1.42] | 0.80 | 1.07 [0.60–1.89] |
A | T | C | 0.51 | 0.78 [0.35–1.87] | 0.05 | 0.50 [0.22–1.05] | 0.66 | 0.85 [0.38–1.83] |
BANK1 | p | OR [95% CI] | p | OR [95% CI] | p | OR [95% CI] | ||
rs10516487 | rs3733197 | |||||||
G | G | - | Ref. | - | Ref. | - | Ref. | |
A | A | 0.96 | 0.99 [0.64–1.54] | 0.82 | 1.04 [0.72–1.51] | 0.24 | 1.25 [0.85–1.82] | |
G | A | 0.40 | 1.33 [0.67–2.83] | 0.72 | 1.01 [0.63–1.93] | 0.51 | 1.20 [0.67–2.11] | |
A | G | 0.57 | 1.26 [0.55–3.26] | 0.28 | 1.43 [0.71–2.93] | 0.82 | 1.08 [0.52–2.18] |
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Batista Liz, J.C.; Genre, F.; Pulito-Cueto, V.; Remuzgo-Martínez, S.; Prieto-Peña, D.; Márquez, A.; Ortego-Centeno, N.; Leonardo, M.T.; Peñalba, A.; Narváez, J.; et al. IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms. J. Clin. Med. 2022, 11, 5577. https://doi.org/10.3390/jcm11195577
Batista Liz JC, Genre F, Pulito-Cueto V, Remuzgo-Martínez S, Prieto-Peña D, Márquez A, Ortego-Centeno N, Leonardo MT, Peñalba A, Narváez J, et al. IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms. Journal of Clinical Medicine. 2022; 11(19):5577. https://doi.org/10.3390/jcm11195577
Chicago/Turabian StyleBatista Liz, Joao Carlos, Fernanda Genre, Verónica Pulito-Cueto, Sara Remuzgo-Martínez, Diana Prieto-Peña, Ana Márquez, Norberto Ortego-Centeno, María Teresa Leonardo, Ana Peñalba, Javier Narváez, and et al. 2022. "IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms" Journal of Clinical Medicine 11, no. 19: 5577. https://doi.org/10.3390/jcm11195577
APA StyleBatista Liz, J. C., Genre, F., Pulito-Cueto, V., Remuzgo-Martínez, S., Prieto-Peña, D., Márquez, A., Ortego-Centeno, N., Leonardo, M. T., Peñalba, A., Narváez, J., Martín-Penagos, L., Belmar-Vega, L., Gómez-Fernández, C., Miranda-Filloy, J. A., Caminal-Montero, L., Collado, P., De Árgila, D., Quiroga-Colina, P., Vicente-Rabaneda, E. F., ... López-Mejías, R. (2022). IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms. Journal of Clinical Medicine, 11(19), 5577. https://doi.org/10.3390/jcm11195577