• Disease
  • Graves Disease
  • Association Of...
  • Title:

    Association of Polymorphism in Genes Encoding κB Inhibitors (IκB) With Susceptibility to and Phenotype of Graves' Disease: A Case-Control Study

    Authors: Tomasz BednarczukAlina KurylowiczJanusz A NaumanPiotr MiśkiewiczEwa BarAndziak
    Year: 2009
    Times cited: 10

    Key People For Graves Disease

    Top KOLs in the world
    Anthony Peter Weetman
    graves disease thyroid cells vitiligo patients
    Aldo Pinchera
    graves disease thyroid carcinoma breast cancer
    David S Cooper
    thyroid cancer graves disease united states
    Luigi BARTALENA,
    graves disease orbital radiotherapy radioiodine therapy
    Laszlo Hegedüs
    thyroid volume graves disease 131i therapy
    Rebecca S Bahn
    graves ophthalmopathy thyrotropin receptor thyroid association

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


    BACKGROUND: Genes related to the nuclear factor-kappaB (NF-kappaB), 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-kappaB inhibitors: IKBL (encoding inhibitor of kappaB-like) and NFKBIA (encoding kappaB inhibitor alpha), 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-kappaB inhibitors may contribute to the development and clinical phenotype of GD.

    Sign-in to see all concepts, it's free!