title: Polymorphisms in the myosin light chain kinase gene that confer risk of severe sepsis are associated with a lower risk of asthma.
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).
  
  
  CONCLUSIONS
  MYLK polymorphisms may function as a common genetic factor in clinically distinct diseases involving bronchial smooth muscle contraction and inflammation.
  
  
  CONCLUSIONS
  Genetic variants in MYLK are significantly associated with both asthma and sepsis in populations of African ancestry.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Audrey V
authors.initials: AV
authors.lastname: Grant
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rafaels
authors.forename: Maria
authors.initials: M
authors.lastname: Stockton-Porter
authors.forename: Tonya
authors.initials: T
authors.lastname: Watkins
authors.forename: Peisong
authors.initials: P
authors.lastname: Gao
authors.forename: Peter
authors.initials: P
authors.lastname: Chi
authors.forename: Melba
authors.initials: M
authors.lastname: Muñoz
authors.forename: Harold
authors.initials: H
authors.lastname: Watson
authors.forename: Georgia
authors.initials: G
authors.lastname: Dunston
authors.forename: Alkis
authors.initials: A
authors.lastname: Togias
authors.forename: Nadia
authors.initials: N
authors.lastname: Hansel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sevransky
authors.forename: James P
authors.initials: JP
authors.lastname: Maloney
authors.forename: Marc
authors.initials: M
authors.lastname: Moss
authors.forename: Carl
authors.initials: C
authors.lastname: Shanholtz
authors.forename: Roy
authors.initials: R
authors.lastname: Brower
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Grigoryev
authors.forename: Christopher
authors.initials: C
authors.lastname: Cheadle
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
mesh_terms: D001741:Black or African American / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D044383:Black People / Q000235:genetics; D017691:Caribbean Region; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D018805:Sepsis / Q000235:genetics*
chemical_list: D009219:Myosin-Light-Chain Kinase