title: Genetic association of key Th1/Th2 pathway candidate genes, IRF2, IL6, IFNGR2, STAT4 and IL4RA, with atopic asthma in the Indian population.
abstract: Asthma is a complex, multifactorial disease resulting due to dysregulated immune responses. Genetic factors contribute significantly to asthma pathogenesis, and identification of these factors is one of the major goals in understanding the disease. Th1/Th2 helper differentiation has a critical role in modulating the phenotypes associated with atopic asthma. This study was aimed at identifying genetic modifiers of asthma in selected genes involved in T helper differentiation. A total of 354 single-nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped in a case-control cohort (cases=147, controls=199) and families (n=247) using Illumina's Golden Gate Assay. Five SNPs, rs3733475A/C (IRF2), rs2069832A/G (IL6), rs2012075G/A (IFNGR2) and rs1400656G/A (STAT4) and rs1805011C/A (IL4RA) were found to be associated with asthma in family based as well as in case-control analyses (P=0.002, P=0.001, P=0.004, P=0.003 and P=0.001, respectively). Interestingly, the minor alleles at these loci showed a protective effect. A five loci haplotype, TAACG, in IRF2 gene, was significantly associated with asthma in families (P=1.1 × 10(-6)) and in case-control cohort (P=0.01). In conclusion, our studies led to identification of some key candidate genes, namely IRF2, IL6, IFNGR2, STAT4 and IL4RA that modulate genetic susceptibility to asthma in the Indian population. Also, this is the first report of independent association of IL6 gene polymorphism with atopic asthma.
authors.affiliation: Molecular Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Amrendra
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Molecular Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Das
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Human Genetics unit, Indian Statistical Institute, Kolkata, India.
authors.forename: Indranil
authors.initials: I
authors.lastname: Mukhopadhyay
authors.affiliation: Molecular Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.|Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007194:India / Q000453:epidemiology; D050836:Interferon Regulatory Factor-2 / Q000235:genetics; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017471:Receptors, Interferon / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D055815:Young Adult
chemical_list: C086185:IFNGR2 protein, human; C504000:IL4R protein, human; C508600:IL6 protein, human; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D053662:Interleukin-4 Receptor alpha Subunit; D015850:Interleukin-6; D017471:Receptors, Interferon; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human