title: Association analysis of signal transducer and activator of transcription 4 (STAT4) polymorphisms with asthma.
abstract: The signal transducer and activator of transcription 4 (STAT4) on chromosome 2q32.2-q32.3 is known to be essential for mediating responses to interleukin 12 in lymphocytes and regulating the differentiation of T helper cells. In an effort to discover additional polymorphism(s) in genes in which variant(s) have been implicated in asthma, we investigated the genetic polymorphisms in STAT4 to evaluate it as a potential candidate gene for a host genetic study of asthma. By direct DNA sequencing in 24 individuals, we identified 12 sequence variants within introns and their flanking regions, including the 1.5 kb promoter region of STAT4. Among them, seven common polymorphic sites were selected for genotyping in our asthma cohort (502 asthmatic patients, 164 normal controls). Using logistic regression analysis for association with the risk of asthma, while controlling for age, gender, and smoking status as covariates, no significant associations with the risk of asthma were detected. However, one single nucleotide polymorphism (SNP) in intron 11 (+90089T--> C) and two haplotypes showed positive association (P= 0.03, 0.03 and 0.03, respectively) with production of specific IgE to Dermatophagoides farinae (D.f.) or Dermatophagoides pteronyssinus (D.p.) among asthmatic patients. The minor allele frequencies of +90089T--> C and BLOCK2-ht1 were higher (0.54 and 0.47, respectively) among individuals who produced specific IgE to D.f. or D.p. than frequencies (0.47 and 0.39, respectively) among individuals who did not produce specific IgE (OR=1.38 and 1.40, respectively). Our findings suggest that polymorphisms in STAT4 might be one of the genetic factors for the risk of production of specific IgE to mite allergens.
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
authors.forename: Yoo Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
authors.forename: Sohg
authors.initials: S
authors.lastname: Namgoong
authors.affiliation: Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea.
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
authors.affiliation: Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea.
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea.
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.affiliation: Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea.
authors.forename: June Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea. mdcspark@unitel.co.kr.|Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, Korea, 420-021. mdcspark@unitel.co.kr.
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000367:Age Factors; D000485:Allergens / Q000235:genetics*; D039741:Antigens, Dermatophagoides / Q000235:genetics* / Q000276:immunology; D001249:Asthma / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D040461:Gene Components; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D007723:Korea; D015810:Linkage Disequilibrium; D016015:Logistic Models; D011110:Polymorphism, Genetic; D050797:STAT4 Transcription Factor; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D012907:Smoking; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators; D007073:Immunoglobulin E
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