Polymorphisms in the myosin light chain kinase gene that confer risk of severe sepsis are associated with a lower risk of asthma.
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.
Gao
Li
L
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA.
Grant
Audrey V
AV
Rafaels
Nicholas
N
Stockton-Porter
Maria
M
Watkins
Tonya
T
Gao
Peisong
P
Chi
Peter
P
Muñoz
Melba
M
Watson
Harold
H
Dunston
Georgia
G
Togias
Alkis
A
Hansel
Nadia
N
Sevransky
Jonathan
J
Maloney
James P
JP
Moss
Marc
M
Shanholtz
Carl
C
Brower
Roy
R
Garcia
Joe G N
JG
Grigoryev
Dmitry N
DN
Cheadle
Christopher
C
Beaty
Terri H
TH
Mathias
Rasika A
RA
Barnes
Kathleen C
KC
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*
D009219:Myosin-Light-Chain Kinase