Abstract
The gene for mast cell chymase (CMA1) is an ideal candidate for investigating genetic predisposition to atopic asthma, as it is an important mediator of inflammation and remodeling in the asthmatic lung. Various studies have examined the association between −1903 G/A polymorphism and allergic phenotypes, but inconsistent results have been obtained. We investigated the association of this SNP and a novel (TG)n(GA)m repeat polymorphism (accession no. BV210164) 254 bp downstream of the gene with asthma and its associated traits in a case-control study in two independent cohorts recruited from the Indian population. A significant association was observed for the (TG)n(GA)m repeat with asthma (p<0.05) in both the cohorts. Although no association was observed for the −1903 G/A SNP with asthma, a significant association was observed between the genotypes and serum IgE levels (p=0.003 and 0.0004 for cohort A and B). When haplotypes were compared between patients and controls, the haplotype G_43 was found at higher frequency in controls (p=0.05). Also, on comparing major haplotypes (>5%) with respect to log total serum IgE levels, a significant difference was obtained (p=0.018 and p=0.046 for cohorts A and B). These results suggest that the CMA1 gene contributes to asthma susceptibility and may be involved in regulating IgE levels in atopic asthma.
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Acknowledgements
We thank our collaborating physicians Drs. S.K. Sharma, Brajen Lahker, Aditi Sinha, Virender Kumar, N.K. Bhatia and P.V. Niphadkar for helping us in sample collection. We also thank all patients, their family members, and healthy volunteers for participating in this study. We thank Ms. Mamta Sharma, Ms. Jyotsna Batra, Mr. Rajshekhar Chatterjee, Ms. Deepti Mann, Ms. Sanober Nahid, and Ms. Sangeeta Goswami for assistance. We acknowledge the Functional Genomics Unit of IGIB, Delhi, for helping in sequencing and genotyping. The financial support from the Council of Scientific and Industrial Research (CSIR), Government of India, is greatly acknowledged.
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Sharma, S., Rajan, U.M., Kumar, A. et al. A novel (TG)n(GA)m repeat polymorphism 254 bp downstream of the mast cell chymase (CMA1) gene is associated with atopic asthma and total serum IgE levels. J Hum Genet 50, 276–282 (2005). https://doi.org/10.1007/s10038-005-0252-x
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DOI: https://doi.org/10.1007/s10038-005-0252-x
