Association analysis of novel TBX21 variants with asthma phenotypes.
Human TBX21 expressed in T Cells (T-BOX21) is a Th1-specific T-box transcription factor that controls the expression of the hallmark Th1 cytokine, IFNG. As a potent candidate gene for asthma genetic study, we have sequenced the full gene of human TBX21, including the -1,500bp promoter region to identify its gene polymorphisms. Twenty-three single nucleotide polymorphisms (SNPs) were identified; one in promoter region (c.-1514T>C), one in 5'UTR (c.-138C>A), two in exon 1 (c.99C>G (p.His33Gln), c.390A>G), sixteen in introns (c.492+806T>C, c.492+1170C>A, c.492+1514G>A, c.492+1907A>C, c.492+2116G>A, c.492+2516A>G, c.492+2953C>T, c.492+4207A>T, c.492+4211A>T, c.492+4985T>A, c.492+4207G>A, c.492+5533C>T, c.492+7889T>A, c.492+8270G>C, c.768+417T>C and c.989+183C>T), one in exon 4 (c.831C>T), one in exon 6 (c.1455G>A), and one in 3'UTR (c.2103A>C). Among twenty-three identified variants, seven were selected for larger scale genotyping (n=721) for asthma association study based on frequencies and location. Haplotypes, their frequencies and linkage disequilibrium coefficients (mid R:D'mid R:) between SNP pairs were estimated. The associations with risk of asthma, skin-test reactivity and total serum IgE levels were analyzed. Using statistical analyses for association of TBX21 polymorphisms with these three asthma phenotypes, no significant signals were detected. In conclusion, we identified twenty-three genetic polymorphisms in the important TBX21 gene, but no significant associations of TBX21 variants with asthma phenotypes were detected. TBX21 variation/haplotype information identified in this study will provide valuable information for future association studies of other immunological diseases.
Chung
Hun Taek
HT
Genomic Research Center for Immune Disorders, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, Korea.
Kim
Lyoung Hyo
LH
Park
Byung Lae
BL
Lee
June Hyuk
JH
Park
Hae-Sim
HS
Choi
Byoung Whui
BW
Hong
Soo-Jong
SJ
Chae
Soo Cheon
SC
Kim
Jeong Joong
JJ
Park
Choon-Sik
CS
Shin
Hyoung Doo
HD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics*; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor