title: Association analysis of novel TBX21 variants with asthma phenotypes.
abstract: 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.
authors.affiliation: Genomic Research Center for Immune Disorders, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, Korea.
authors.forename: Hun Taek
authors.initials: HT
authors.lastname: Chung
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: June Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Hong
authors.forename: Soo Cheon
authors.initials: SC
authors.lastname: Chae
authors.forename: Jeong Joong
authors.initials: JJ
authors.lastname: Kim
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 / 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
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor