Novel association in chromosome 4q27 region with rheumatoid arthritis and confirmation of type 1 diabetes point to a general risk locus for autoimmune diseases - PubMed (original) (raw)

doi: 10.1086/522037. Epub 2007 Oct 24.

Behrooz Z Alizadeh, Marianna Bevova, Miek A van Leeuwen, Marieke J H Coenen, Barbara Franke, Lude Franke, Marcel D Posthumus, David A van Heel, Gerrit van der Steege, Timothy R D J Radstake, Pilar Barrera, Bart O Roep, Bobby P C Koeleman, Cisca Wijmenga

Affiliations

Novel association in chromosome 4q27 region with rheumatoid arthritis and confirmation of type 1 diabetes point to a general risk locus for autoimmune diseases

Alexandra Zhernakova et al. Am J Hum Genet. 2007 Dec.

Abstract

Recently, association of celiac disease with common single-nucleotide polymorphism (SNP) variants in an extensive linkage-disequilibrium block of 480 kb containing the KIAA1109, Tenr, IL2, and IL21 genes has been demonstrated in three independent populations (rs6822844P combined=1.3 x 10(-14)). The KIAA1109/Tenr/IL2/IL21 block corresponds to the Idd3 locus in the nonobese diabetic mouse model of type 1 diabetes (T1D). This block was recently found to be associated with T1D in a genomewide association study, although this finding lacks unequivocal confirmation. We therefore aimed to investigate whether the KIAA1109/Tenr/IL2/IL21 region is involved in susceptibility to multiple autoimmune diseases. We tested SNP rs6822844 for association with disease in 350 T1D-affected and 1,047 rheumatoid arthritis (RA)-affected Dutch patients and in 929 controls. We replicated the association with T1D (P=.0006; OR 0.64 [95% CI 0.50-0.83]), and revealed a similar novel association with RA (P=.0002; OR 0.72 [95% CI 0.61-0.86]). Our results replicate and extend the association found in the KIAA1109/Tenr/IL2/IL21 gene region with autoimmune diseases, implying that this locus is a general risk factor for multiple autoimmune diseases.

PubMed Disclaimer

Figures

Figure 1.

Figure 1.

The frequency of rs6822844 and rs4505848 alleles in Dutch AIDs cohorts and controls and in a meta-analysis of Dutch, U.K., and Irish AIDs cohorts. Dutch AIDs cohorts include T1D (

_n_=670

), CD (

_n_=1,012

), and RA (

_n_=2,024

). Data for the U.K. and Irish cohorts were extracted from the work of van Heel et al. n = Number of chromosomes. ORs and the corresponding 95% CIs were estimated using a random-effect model. Vertical lines represent no effect (i.e., disease risk = 1).

References

Web Resources

    1. HapMap, http://www.hapmap.org/ (for information about SNPs and LD in population controls)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for T1D, RA, CD, PTPN22, CTLA4, IL2, IL21, and CD25)

References

    1. Lin JP, Cash JM, Doyle SZ, Peden S, Kanik K, Amos CI, Bale SJ, Wilder RL (1998) Familial clustering of rheumatoid arthritis with other autoimmune diseases. Hum Genet 103:475–48210.1007/s004390050853 - DOI - PubMed
    1. Levin L, Tomer Y (2003) The etiology of autoimmune diabetes and thyroiditis: evidence for common genetic susceptibility. Autoimmun Rev 2:377–38610.1016/S1568-9972(03)00080-6 - DOI - PubMed
    1. Tait KF, Marshall T, Berman J, Carr-Smith J, Rowe B, Todd JA, Bain SC, Barnett AH, Gough SC (2004) Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren repository. Diabet Med 21:358–36210.1111/j.1464-5491.2004.01162.x - DOI - PubMed
    1. Barera G, Bonfanti R, Viscardi M, Bazzigaluppi E, Calori G, Meschi F, Bianchi C, Chiumello G (2002) Occurrence of celiac disease after onset of type 1 diabetes: a 6-year prospective longitudinal study. Pediatrics 109:833–83810.1542/peds.109.5.833 - DOI - PubMed
    1. Brand O, Gough S, Heward J (2005) HLA, CTLA-4 and PTPN22: the shared genetic master-key to autoimmunity? Expert Rev Mol Med 7:1–1510.1017/S1462399405009981 - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources