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
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA.
J Allergy Clin Immunol. 2007 May;119(5):1111-8. doi: 10.1016/j.jaci.2007.03.019.
Myosin light chain kinase (MYLK) is a multifunctional protein involved in regulation of airway hyperreactivity and other activities relevant to asthma.
To determine the role of MYLK gene variants in asthma among African Caribbean and African American populations.
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.
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).
MYLK polymorphisms may function as a common genetic factor in clinically distinct diseases involving bronchial smooth muscle contraction and inflammation.
Genetic variants in MYLK are significantly associated with both asthma and sepsis in populations of African ancestry.
肌球蛋白轻链激酶（MYLK）是一种多功能蛋白，参与气道高反应性调节及其他与哮喘相关的活动。
确定MYLK基因变异在非洲裔加勒比人和非裔美国人哮喘中的作用。
我们在2个独立的、基于家系的非洲裔人群中，对MYLK基因单核苷酸多态性（SNP）与哮喘易感性及总血清IgE浓度进行了关联测试。此前我们已鉴定出MYLK中赋予败血症和急性肺损伤风险的变异/单倍型；我们将哮喘人群的研究结果与非裔美国人败血症和急性肺损伤组的结果进行了比较。
在非洲裔加勒比人家系中观察到MYLK SNP与哮喘及总血清IgE浓度之间存在显著关联：平滑肌形式的一个启动子SNP（rs936170）关联最强（P = 0.009）。一个包含rs936170的单倍型，对应非肌肉和平滑肌形式的肌动蛋白结合活性，在美国（P = 0.005）和加勒比人家系（P = 0.004）中均与哮喘呈负相关（即风险降低），且与赋予严重败血症风险的单倍型相同（P = 0.002）。对PBMC和rs936170的RNA表达研究表明，携带此变异的哮喘患者中MYLK表达显著降低（P = 0.025）。
MYLK多态性可能是涉及支气管平滑肌收缩和炎症的临床不同疾病中的一个共同遗传因素。
MYLK基因变异在非洲裔人群中与哮喘和败血症均显著相关。
