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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, p c  = 0.07, OR = 1.65 [95%CI: 1.18-2.38] and p = 0.002, p c  = 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.

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