MYLK polymorphism associated with blood eosinophil level among asthmatic patients in a Korean population.
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.
Lee
Soo Ok
SO
Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, 153-803, Korea.
Cheong
Hyun Sub
HS
Park
Byung Lae
BL
Bae
Joon Seol
JS
Sim
Won Chul
WC
Chun
Ji-Yong
JY
Isbat
Mohammad
M
Uh
Soo-Taek
ST
Kim
Yong Hooun
YH
Jang
An-Soo
AS
Park
Choon-Sik
CS
Shin
Hyoung Doo
HD
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
D002135:Calcium-Binding Proteins; C499378:MYLK protein, human; D009219:Myosin-Light-Chain Kinase