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Thyroid Research
Published in: Thyroid Research 1/2009

Open Access 01-12-2009 | Research

Association of polymorphism in genes encoding κB inhibitors (IκB) with susceptibility to and phenotype of Graves' disease: a case-control study

Authors: Alina Kurylowicz, Piotr Miśkiewicz, Ewa Bar-Andziak, Janusz Nauman, Tomasz Bednarczuk

Published in: Thyroid Research | Issue 1/2009

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Abstract

Background

Genes related to the nuclear factor-κB (NF-κB), a key transcription factor involved in regulation of immune responses, are interesting candidates for association studies in autoimmune disorders. The aim of this study was to investigate an association of polymorphisms in two genes encoding NF-κB inhibitors: IKBL (encoding inhibitor of κB-like) and NFKBIA (encoding κB inhibitor α), withsusceptibility to and phenotype of Graves' disease (GD).

Methods

A population-based, case-control association study comprising 481 patients with GD and 455 healthy controls was performed. We analyzed 3 single nucleotide polymorphisms (SNPs) in IKBL [promoter region -62T/A substitution (rs2071592), intron 1 C/T substitution (rs2071591) and exon 4 T/C substitution (rs3130062)] and 3 SNPs in NFKBIA [G/A substitution in 3' untranslated region (rs696) and two promoter region polymorphisms -297C/T (rs2233409) and -826C/T (rs2233406)] by the PCR-restriction fragment length polymorphism (RFLP) method.

Results

The two SNPs in IKBL (rs2071592 and rs2071591) were in a strong linkage disequilibrium (D' = 0.835) and the AT haplotype was associated with susceptibility to GD (p < 10-4, OR = 1.61 [95%CI:1.21-2.14]). Moreover subgroup analysis revealed a gen-gen interaction between the investigated IKBL haplotype and HLA-DRB1*03 allele (p < 10-4). The investigated NFKBIA SNPs were not associated with susceptibility to GD. However, when correlated with phenotype, the -297T (rs2233409) and -826T (rs2233406) alleles were associated with the development of clinically evident ophthalmophaty (p = 0.004, pc = 0.07, OR = 1.65 [95%CI: 1.18-2.38] and p = 0.002, pc = 0.036, OR = 1.67 [95%CI: 1.20-2.36], respectively).

Conclusion

Our results suggest that SNPs in genes encoding NF-κB inhibitors may contribute to the development and clinical phenotype of GD.
Appendix
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Metadata
Title
Association of polymorphism in genes encoding κB inhibitors (IκB) with susceptibility to and phenotype of Graves' disease: a case-control study
Authors
Alina Kurylowicz
Piotr Miśkiewicz
Ewa Bar-Andziak
Janusz Nauman
Tomasz Bednarczuk
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Thyroid Research / Issue 1/2009
Electronic ISSN: 1756-6614
DOI
https://doi.org/10.1186/1756-6614-2-10

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