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KMID : 0578320090270020175
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Molecules and Cells
2009 Volume.27 No. 2 p.175 ~ p.181
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MYLK Polymorphism Associated with Blood Eosinophil Level among Asthmatic Patients in a Korean Population
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Lee Soo-Ok
Cheong Hyun-Sub
Park Byung-Lae
Bae Joon-Seol
Sim Won-Chul
Chun Ji-Yong
Isbat Mohammad
Kim Yong-Hooun
Uh Soo-Taek
Jang An-Soo
Park Choon-Sik
Shin Hyoung-Doo
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Abstract
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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/genotyp-ing and statistical analysis in Korean population (n = 1,015). Seventeen common polymorphisms located in or near exons, having pairwise r2 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/Pcorr = 0.01 and P = 0.002/Pcorr = 0.01, respectively). The log-trans-formed 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-trans-formed 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.
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KEYWORD
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Asthma, Eosinophil, myosin light chain kinase, polymorphism
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