Association analysis of signal transducer and activator of transcription 4 (STAT4) polymorphisms with asthma.
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.
Park
Byung Lae
BL
Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
Cheong
Hyun Sub
HS
Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
Kim
Lyoung Hyo
LH
Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
Choi
Yoo Hyun
YH
Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
Namgoong
Sohg
S
Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
Park
Hae-Sim
HS
Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea.
Hong
Soo-Jong
SJ
Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea.
Choi
Byoung Whui
BW
Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea.
Lee
June Hyuk
JH
Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital, and Choong-Ang University Hospital, Korea.
Park
Choon-Sik
CS
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.
Shin
Hyoung Doo
HD
Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea, 110-834.
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*
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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