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).

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.

• Authors: 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 Cheadle, Terri H Beaty, Rasika A Mathias, Kathleen C Barnes
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 119 Issue 5 Pg. 1111-8 (May 2007) ISSN: 0091-6749 [Print] United States
• PMID: 17472811 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Myosin-Light-Chain Kinase

Topics

• Black or African American (genetics)
• Asthma (genetics)
• Black People (genetics)
• Caribbean Region
• Female
• Genetic Predisposition to Disease
• Humans
• Male
• Myosin-Light-Chain Kinase (genetics)
• Polymorphism, Single Nucleotide
• Risk Factors
• Sepsis (genetics)