RESUMO
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 disease involving broanchial smooth muscle contraction and inflammation. CLINICAL IMPLICATIONS: Genetic variants in MYLK are significantly associated with both asthma and sepsis in populations of African ancestry (AU)