title: MYLK polymorphism associated with blood eosinophil level among asthmatic patients in a Korean population.
abstract: 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.
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, 153-803, Korea.
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Won Chul
authors.initials: WC
authors.lastname: Sim
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Chun
authors.forename: Mohammad
authors.initials: M
authors.lastname: Isbat
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Yong Hooun
authors.initials: YH
authors.lastname: Kim
authors.forename: An-Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009219:Myosin-Light-Chain Kinase / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D002135:Calcium-Binding Proteins; C499378:MYLK protein, human; D009219:Myosin-Light-Chain Kinase