Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis

  • Authors:
    • Yang An
    • Hidenori Ohnishi
    • Eiko Matsui
    • Michinori Funato
    • Zenichiro Kato
    • Takahide Teramoto
    • Hideo Kaneko
    • Takeshi Kimura
    • Kazuo Kubota
    • Kimiko Kasahara
    • Naomi Kondo
  • View Affiliations

  • Published online on: March 8, 2011     https://doi.org/10.3892/ijmm.2011.645
  • Pages: 795-801
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Abstract

Toll-like receptors (TLRs) are important pathogen-associated molecular pattern recognition receptors involved in initiating immune responses. The adaptor protein MyD88 adaptor-like (Mal), involved in signaling downstream of TLRs, plays a crucial role in mediating NF-κB activation. The association of Mal polymorphisms with allergic diseases has not previously been defined. The objective of this study was to detect polymorphisms in the Mal gene and to investigate their association with allergic diseases. Mal gene polymorphisms were genotyped in 310 subjects. The functional effects of Mal variants were analyzed in vitro. One Mal polymorphism, c.303 G>A (Q101Q), was found at a significantly lower frequency in atopic dermatitis patients (p=0.016). Q101Q is in linkage disequilibrium with -103 A>G (rs1893352) and c.539 C>T (S180L) (rs8177374) in the HapMap database. The A allele of -103 A>G showed significantly reduced transcription of Mal compared with the G allele. In addition, three rare variants were identified in this study, c.394 G>A (E132K), c.428 G>A (R143Q) and c.570 G>C (E190D), and were shown to lead to loss-of-function of Mal. It is possible that gene polymorphisms in Mal could affect atopic dermatitis by influencing the innate immune system. We show that Q101Q, which is in linkage disequilibrium with -103 A>G and S180L, may play a protective role against atopic dermatitis. Furthermore, we propose that loss-of-function variants of Mal could predispose individuals to atopic dermatitis or other immunological disorders.

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June 2011
Volume 27 Issue 6

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

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Spandidos Publications style
An Y, Ohnishi H, Matsui E, Funato M, Kato Z, Teramoto T, Kaneko H, Kimura T, Kubota K, Kasahara K, Kasahara K, et al: Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis. Int J Mol Med 27: 795-801, 2011
APA
An, Y., Ohnishi, H., Matsui, E., Funato, M., Kato, Z., Teramoto, T. ... Kondo, N. (2011). Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis. International Journal of Molecular Medicine, 27, 795-801. https://doi.org/10.3892/ijmm.2011.645
MLA
An, Y., Ohnishi, H., Matsui, E., Funato, M., Kato, Z., Teramoto, T., Kaneko, H., Kimura, T., Kubota, K., Kasahara, K., Kondo, N."Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis". International Journal of Molecular Medicine 27.6 (2011): 795-801.
Chicago
An, Y., Ohnishi, H., Matsui, E., Funato, M., Kato, Z., Teramoto, T., Kaneko, H., Kimura, T., Kubota, K., Kasahara, K., Kondo, N."Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis". International Journal of Molecular Medicine 27, no. 6 (2011): 795-801. https://doi.org/10.3892/ijmm.2011.645