Polymorphisms in the myosin light chain kinase gene that confer risk of severe sepsis are associated with a lower risk of asthma

Li Gao, Audrey V. Grant, Nicholas Rafaels, Maria Stockton-Porter, Tonya Watkins, Peisong Gao, Peter Chi, Melba Muñoz, Harold Watson, Georgia Dunston, Alkis Togias, Nadia Hansel, Jonathan Sevransky, James P. Maloney, Marc Moss, Carl Shanholtz, Roy Brower, Joe G.N. Garcia, Dmitry N. Grigoryev, Christopher CheadleTerri H. Beaty, Rasika A. Mathias, Kathleen C. Barnes

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Background: Myosin light chain kinase (MYLK) is a multifunctional protein involved in regulation of airway hyperreactivity and other activities relevant to asthma. Objective: To determine the role of MYLK gene variants in asthma among African Caribbean and African American populations. Methods: We performed association tests between single nucleotide polymorphisms (SNPs) in the MYLK gene and asthma susceptibility and total serum IgE concentrations in 2 independent, family-based populations of African descent. Previously we identified variants/haplotypes in MYLK that confer risk for sepsis and acute lung injury; we compared findings from our asthma populations to findings in the African American sepsis and acute lung injury groups. Results: Significant associations between MYLK SNPs and asthma and total serum IgE concentrations were observed in the African Caribbean families: a promoter SNP (rs936170) in the smooth muscle form gave the strongest association (P = .009). A haplotype including rs936170 corresponding to the actin-binding activity of the nonmuscle and smooth muscle forms was negatively associated with asthma (eg, decreased risk) in both the American (P = .005) and Caribbean families (P = .004), and was the same haplotype that conferred risk for severe sepsis (P = .002). RNA expression studies on PBMCs and rs936170 suggested a significant decrease in MYLK expression among patients with asthma with this variant (P = .025). Conclusion: MYLK polymorphisms may function as a common genetic factor in clinically distinct diseases involving bronchial smooth muscle contraction and inflammation. Clinical implications: Genetic variants in MYLK are significantly associated with both asthma and sepsis in populations of African ancestry.

Original languageEnglish (US)
Pages (from-to)1111-1118
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume119
Issue number5
DOIs
StatePublished - May 2007

Keywords

  • ALI
  • MYLK/MLCK
  • SNPs
  • asthma
  • haplotype
  • sepsis
  • total IgE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gao, L., Grant, A. V., Rafaels, N., Stockton-Porter, M., Watkins, T., Gao, P., Chi, P., Muñoz, M., Watson, H., Dunston, G., Togias, A., Hansel, N., Sevransky, J., Maloney, J. P., Moss, M., Shanholtz, C., Brower, R., Garcia, J. G. N., Grigoryev, D. N., ... Barnes, K. C. (2007). Polymorphisms in the myosin light chain kinase gene that confer risk of severe sepsis are associated with a lower risk of asthma. Journal of Allergy and Clinical Immunology, 119(5), 1111-1118. https://doi.org/10.1016/j.jaci.2007.03.019