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

Gao, Li; Grant, Audrey V; Rafaels, Nicholas; Stockton-Porter, Maria; Watkins, Tonya; Gao, Peisong; Chi, Peter; Muñoz, Melba; Watson, Harold; Dunston, Georgia; Togias, Alkis; Hansel, Nadia; Sevransky, Jonathan; Maloney, James P; Moss, Marc; Shanholtz, Carl; Brower, Roy; Garcia, Joe G N; Grigoryev, Dmitry N; Cheadle, Christopher; Beaty, Terri H; Mathias, Rasika A; Barnes, Kathleen C.
J Allergy Clin Immunol; 119(5): 1111-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17472811

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.
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