期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 119, 期 5, 页码 1111-1118出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2007.03.019
关键词
SNPs; haplotype; MYLK/MLCK; asthma; total IgE; sepsis; ALI
资金
- Intramural NIH HHS Funding Source: Medline
- NHLBI NIH HHS [HL 73994, U01 HL72455, U01 HL66615] Funding Source: Medline
- NIAID NIH HHS [AI50024-03, HL/AI-49612] Funding Source: Medline
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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