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Association analysis of signal transducer and activator of transcription 4 (STAT4) polymorphisms with asthma.

Park, BL; Cheong, HS; Kim, LH; Choi, YH; Namgoong, S; Park, HS; Hong, SJ; Choi, BW; Lee, JH; Park, CS; Shin, HD
Journal of human genetics, 50(3):133-138, 2005
Journal Title
Journal of human genetics
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.
MeSH terms
Age FactorsAllergens/genetics*Antigens, Dermatophagoides/genetics*Antigens, Dermatophagoides/immunologyAsthma/genetics*Chromosomes, Human, Pair 2/genetics*DNA PrimersDNA-Binding Proteins/genetics*Gene ComponentsGene FrequencyGenotypeHumansImmunoglobulin E/geneticsImmunoglobulin E/immunologyKoreaLinkage DisequilibriumLogistic ModelsPolymorphism, Genetic*STAT4 Transcription FactorSequence Analysis, DNASex FactorsSmokingTrans-Activators/genetics*
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Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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