MYLK polymorphism associated with blood eosinophil level among asthmatic patients in a Korean population
MYLK polymorphism associated with blood eosinophil level among asthmatic patients in a Korean population
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DOI：
10.1007/s10059-009-0022-2
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发表时间：
2009-02-01
影响因子：
3.8
通讯作者：
Shin, Hyoung Doo
中科院分区：
文献类型：
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作者：
Lee, Soo Ok;Cheong, Hyun Sub;Shin, Hyoung Doo
肌球蛋白轻链激酶 (MYLK) 基因编码平滑肌和非肌肉细胞亚型。最近，据报道 MYLK 的多态性与多种疾病相关。为了检查多态性对哮喘风险和相关表型的遗传影响，我们通过对韩国人群（n = 1,015）进行重新测序/基因分型和统计分析来仔细检查 MYLK。对位于外显子内或附近的 17 个常见多态性进行了基因分型，其成对 r (2) 值小于 0.25。我们的统计分析并未复制非洲后裔人群中观察到的哮喘风险和对数转换总 IgE 水平之间的关联。然而，内含子 16 中的两个 SNP（+89872C > G 和 +92263T > C）处于紧密 LD (|D'| = 0.99) 状态，即使在校正多重测试后，也显示与对数转换的血液嗜酸性粒细胞水平显着相关（P = 0.002/P (corr) = 0.01 和 P = 0.002/P (corr) = 0.01，分别）。携带 +89872C > G 和 +92263T > C 次要等位基因的个体的对数转换血液嗜酸性粒细胞水平高于携带其他等位基因的个体。在额外的亚组分析中，两种 SNP 的遗传效应在哮喘患者和特应性哮喘患者中更为明显。在特应性哮喘患者中，+89872C > G 和 +92263T > C 中，对数转换的血液嗜酸性粒细胞水平以基因剂量依赖性方式按比例增加（分别为 P = 0.0002 和 P = 0.00007）。这些发现表明，MYLK 多态性可能是哮喘患者血液嗜酸性粒细胞水平差异性升高的遗传因素之一。需要进一步的生物学和/或功能研究来证实我们的结果。
The myosin light chain kinase (MYLK) gene encodes both smooth muscle and nonmuscle cell isoforms. Recently, polymorphisms in MYLK have been reported to be associated with several diseases. To examine the genetic effects of polymorphisms on the risk of asthma and related phenotypes, we scrutinized MYLK by re-sequencing/genotyping and statistical analysis in Korean population (n = 1,015). Seventeen common polymorphisms located in or near exons, having pairwise r (2) values less than 0.25, were genotyped. Our statistical analysis did not replicate the associations with the risk of asthma and log-transformed total IgE levels observed among African descendant populations. However, two SNPs in intron 16 (+89872C > G and +92263T > C), which were in tight LD (|D'| = 0.99), revealed significant association with log-transformed blood eosinophil level even after correction multiple testing (P = 0.002/P (corr) = 0.01 and P = 0.002/P (corr) = 0.01, respectively). The log-transformed blood eosinophil levels were higher in individuals bearing the minor alleles for +89872C > G and +92263T > C, than in those bearing other allele. In additional subgroup analysis, the genetic effects of both SNPs were much more apparent among asthmatic patients and atopic asthma patients. Among atopic asthma patients, the log-transformed blood eosinophil levels were proportionally increased by gene-dose dependent manner of in both +89872C > G and +92263T > C (P = 0.0002 and P = 0.00007, respectively). These findings suggest that MYLK polymorphisms might be among the genetic factors underlying differential increases of blood eosinophil levels among asthmatic patients. Further biological and/or functional studies are needed to confirm our results.