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  • Title: Association of NFKB1 -94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves' disease.
    Author: Kurylowicz A, Hiromatsu Y, Jurecka-Lubieniecka B, Kula D, Kowalska M, Ichimura M, Koga H, Kaku H, Bar-Andziak E, Nauman J, Jarzab B, Ploski R, Bednarczuk T.
    Journal: Genes Immun; 2007 Oct; 8(7):532-8. PubMed ID: 17690684.
    Abstract:
    Recently, a functional polymorphism in the NFKB1 gene promoter (-94ins/del ATTG) has been identified and associated with chronic inflammatory diseases. The aim of this study was to analyze the association of NFKB1 polymorphism with susceptibility to and phenotype of Graves' disease (GD). The initial case-control association study, performed in a Polish-Warsaw cohort (388 GD patients and 688 controls), was followed by the two replication studies performed in Polish-Gliwice and Japanese-Kurume cohorts (198 GD patients and 194 controls, and 424 GD patients and 222 controls, respectively). The frequency of the -94del ATTG (D) allele was increased in GD compared to controls in Warsaw cohort. This finding was replicated in Gliwice cohort. Combining both Polish-Caucasian cohorts showed that the NFKB1 polymorphism was significantly associated with susceptibility to GD with a codominant mode of inheritance (P=0.00005; OR=1.37 (1.18-1.60)). No association with GD was found in Japanese cohort. However, subgroup analysis in Japanese GD patients revealed a correlation between the NFKB1genotype and the development of ophthalmopathy (P=0.009; OR=1.49 (1.10-2.01)), and the age of disease onset (P=0.009; OR=1.45 (1.09-1.91)). Our results suggest that NFKB1 -94ins/del ATTG polymorphism may be associated with susceptibility to and/or phenotype of GD.
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