β-2-Adrenergic receptor gene polymorphism confers susceptibility to Graves disease

  • Authors:
    • Krystian Jazdzewski
    • Tomasz Bednarczuk
    • Magdalena Stepnowska
    • Sandya Liyanarachchi
    • Krystyna Suchecka-Rachon
    • Janusz Limon
    • Krzysztof Narkiewicz
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijmm.19.1.181
  • Pages: 181-186
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Abstract

Graves disease (GD) is an autoimmune disorder with genetic predisposition. The polymorphisms 47A↷G (Arg16Gly) and 79C↷G (Gln27Glu) of the adrenergic β-2 receptor (ADRB2) gene in the 5q32 region affect the functional reaction to adrenergic stimulation, which contributes to the regulation of immunological response. The -367T↷C polymorphism within the 5'-leading regulatory sequence affects ADRB2 transcriptional activity. The aim of the present study was to investigate whether ADRB2 gene variants are associated with susceptibility to GD. All polymorphisms were studied in Polish GD patients (n=300) and healthy control subjects without a family history of autoimmune disorders (n=301). Genotypes were determined by the MassARRAY™ system (Sequenom, San Diego, CA). Gly16 and Gln27 allele frequencies were 61.4% and 55.2% among healthy controls, almost the same as previously reported in 4441 white participants of a cardiovascular health study. We found a higher risk of GD in Gln27 carriers (CC or CG genotypes) than in Glu27 homozygous (GG genotype) participants (OR=1.99, 95% CI: 1.27-3.12, p=0.003, pcorr=0.03). The frequency of the 79GG protective genotype was significantly smaller in the GD patients without symptoms of Graves ophthalmopathy compared to controls (10% vs 22%, OR=0.41, 95% CI: 0.234-0.706, p=0.0017, pcorr=0.015). We didn't find any association of -367T↷C or 47A↷G genotypes/alleles with Graves disease, however, haplotype analysis has shown a significant difference in haplotype distribution between patients and controls (the global p=0.001) with increased -367T/47A/79C haplotype frequency in GD patients compared to controls (34% vs 25%, p=0.00073, pcorr=0.0044). In conclusion, Gln27 carriers (79CC or 79GC genotypes) have increased risk of Graves disease. Our results suggest that ADRB2 plays a role in susceptibility to Graves disease in humans.

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January 2007
Volume 19 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Jazdzewski K, Bednarczuk T, Stepnowska M, Liyanarachchi S, Suchecka-Rachon K, Limon J and Narkiewicz K: β-2-Adrenergic receptor gene polymorphism confers susceptibility to Graves disease. Int J Mol Med 19: 181-186, 2007.
APA
Jazdzewski, K., Bednarczuk, T., Stepnowska, M., Liyanarachchi, S., Suchecka-Rachon, K., Limon, J., & Narkiewicz, K. (2007). β-2-Adrenergic receptor gene polymorphism confers susceptibility to Graves disease. International Journal of Molecular Medicine, 19, 181-186. https://doi.org/10.3892/ijmm.19.1.181
MLA
Jazdzewski, K., Bednarczuk, T., Stepnowska, M., Liyanarachchi, S., Suchecka-Rachon, K., Limon, J., Narkiewicz, K."β-2-Adrenergic receptor gene polymorphism confers susceptibility to Graves disease". International Journal of Molecular Medicine 19.1 (2007): 181-186.
Chicago
Jazdzewski, K., Bednarczuk, T., Stepnowska, M., Liyanarachchi, S., Suchecka-Rachon, K., Limon, J., Narkiewicz, K."β-2-Adrenergic receptor gene polymorphism confers susceptibility to Graves disease". International Journal of Molecular Medicine 19, no. 1 (2007): 181-186. https://doi.org/10.3892/ijmm.19.1.181