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.
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Acknowledgements
We acknowledge Council of Scientific and Industrial Research, Government of India for financial assistance (BSC0116 & MLP5502) and Department of Science and Technology (GAP84). AK, SD are supported by CSIR senior research fellowship. We thank all participating clinicians; Dr SK Sharma Dr VK Vijayan, Dr PV Niphadkar, Dr B Lahker, Dr A Sinha, Dr U Mabalirajan and volunteers for helping in this study. We also thank Ms Rakhi Sharma, Ms Sanober Nahid, Mr Tej Pratap, Ms Reenu Rajpoot and Ms Deepti Maan for their technical assistance, and Ms Rituparna Chaudhuri for preparation of the final manuscript. Help provided by the genotyping facility and computation facility, CSIR-IGIB is duly acknowledged.
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Kumar, A., Das, S., Agrawal, A. et al. Genetic association of key Th1/Th2 pathway candidate genes, IRF2, IL6, IFNGR2, STAT4 and IL4RA, with atopic asthma in the Indian population. J Hum Genet 60, 443–448 (2015). https://doi.org/10.1038/jhg.2015.45
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DOI: https://doi.org/10.1038/jhg.2015.45
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