Top

Published in:

Open Access 01-12-2006 | Research article

A functional PTPN22polymorphism associated with several autoimmune diseases is not associated with IgA deficiency in the Spanish population

Authors: Concepción Núñez, Raquel López-Mejías, Alfonso Martínez, M Cruz García-Rodríguez, Miguel Fernández-Arquero, Emilio G de la Concha, Elena Urcelay

Published in: BMC Medical Genetics | Issue 1/2006

Abstract

Background

The 1858C/T SNP of the PTPN22 gene has been associated with many autoimmune diseases, suggesting the existence of an inflammatory process common to all of them. We studied the association of that polymorphism with immunoglobulin A deficiency (IgAD) following a double approach: a case-control and a TDT study.

Methods

A total of 259 IgAD patients and 455 unrelated matched controls, and 128 families were used for each approach. Comparisons were performed using Chi-Square tests or Fisher's exact test when necessary.

Results

No association between the PTPN22 1858C/T SNP and IgA deficiency was found in any case (allelic frequencies 8% vs. 6% in patients and controls, respectively, OR= 1.14 (0.72–1.79), p= 0.56; TDT p = 0.08).

Conclusion

The result obtained seems to reinforce the consideration of IgA deficiency as a primary immunodeficiency rather than an autoimmune disease.

Burrows PD, Cooper MD: IgA deficiency. Adv Immunol. 1997, 65: 245-276.CrossRefPubMed

De la Concha EG, Fernandez-Arquero M, Gual L, Vigil P, Martinez A, Urcelay E, Ferreira A, Garcia-Rodriguez MC, Fontan G: MHC susceptibility genes to IgA deficiency are located in different regions on different HLA haplotypes. J Immunol. 2002, 169 (8): 4637-4643.CrossRefPubMed

Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS: TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005, 37 (8): 829-834. 10.1038/ng1601.CrossRefPubMed

Kralovicova J, Hammarstrom L, Plebani A, Webster AD, Vorechovsky I: Fine-scale mapping at IGAD1 and genome-wide genetic linkage analysis implicate HLA-DQ/DR as a major susceptibility locus in selective IgA deficiency and common variable immunodeficiency. J Immunol. 2003, 170 (5): 2765-2775.CrossRefPubMed

Siminovitch KA: PTPN22 and autoimmune disease. Nat Genet. 2004, 36 (12): 1248-1249. 10.1038/ng1204-1248.CrossRefPubMed

Criswell LA, Pfeiffer KA, Lum RF, Gonzales B, Novitzke J, Kern M, Moser KL, Begovich AB, Carlton VE, Li W, Lee AT, Ortmann W, Behrens TW, Gregersen PK: Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. Am J Hum Genet. 2005, 76 (4): 561-571. 10.1086/429096.CrossRefPubMedPubMedCentral

Primary immunodeficiency diseases. Report of a WHO scientific group. Immunodefic Rev. 1992, 3 (3): 195-236.

Dupont WD, Plummer WD: Power and sample size calculations for studies involving linear regression. Control Clin Trials. 1998, 19 (6): 589-601. 10.1016/S0197-2456(98)00037-3.CrossRefPubMed

Ewens WJ, Spielman RS: The transmission/disequilibrium test: history, subdivision, and admixture. Am J Hum Genet. 1995, 57 (2): 455-464.PubMedPubMedCentral

10.

Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, Ardlie KG, Huang Q, Smith AM, Spoerke JM, Conn MT, Chang M, Chang SY, Saiki RK, Catanese JJ, Leong DU, Garcia VE, McAllister LB, Jeffery DA, Lee AT, Batliwalla F, Remmers E, Criswell LA, Seldin MF, Kastner DL, Amos CI, Sninsky JJ, Gregersen PK: A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet. 2004, 75 (2): 330-337. 10.1086/422827.CrossRefPubMedPubMedCentral

11.

Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, Eisenbarth GS, Comings D, Mustelin T: A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet. 2004, 36 (4): 337-338. 10.1038/ng1323.CrossRefPubMed

12.

Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW: Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet. 2004, 75 (3): 504-507. 10.1086/423790.CrossRefPubMedPubMedCentral

13.

Cyster JG, Hartley SB, Goodnow CC: Competition for follicular niches excludes self-reactive cells from the recirculating B-cell repertoire. Nature. 1994, 371 (6496): 389-395. 10.1038/371389a0.CrossRefPubMed

14.

Arkwright PD, Abinun M, Cant AJ: Autoimmunity in human primary immunodeficiency diseases. Blood. 2002, 99 (8): 2694-2702. 10.1182/blood.V99.8.2694.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/7/25/prepub

Title: A functional PTPN22polymorphism associated with several autoimmune diseases is not associated with IgA deficiency in the Spanish population
Authors: Concepción Núñez
Raquel López-Mejías
Alfonso Martínez
M Cruz García-Rodríguez
Miguel Fernández-Arquero
Emilio G de la Concha
Elena Urcelay
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2006
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-7-25

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A functional PTPN22polymorphism associated with several autoimmune diseases is not associated with IgA deficiency in the Spanish population

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2006

Deletions in the Y-derived amelogenin gene fragment in the Indian population

Analysis of common PTPN1gene variants in type 2 diabetes, obesity and associated phenotypes in the French population

A novel mutation in the SH3BP2 gene causes cherubism: case report

Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma

Evidence for the association of the SLC22A4 and SLC22A5 genes with Type 1 Diabetes: a case control study

Gene by environment QTL mapping through multiple trait analyses in blood pressure salt-sensitivity: identification of a novel QTL in rat chromosome 5