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Background: Atopic asthma, the most common chronic disease affecting children and young adults, is a complex disorder with variable phenotypes. Cysteine leukotrienes (Cys-LTs) are powerful bronchoconstrictors and play a critical role in airway inflammation and remodeling that are characteristic of asthma. Objective: To investigate the association of ALOX5, LTC4S and CysLTR2 gene polymorphisms with atopic asthma in an Indian population. Methods: A total of 19 single nucleotide polymorphisms (SNPs) within these genes were genotyped in a family-based cohort (n = 239) and a case-control cohort (139 cases and 194 controls) followed by association analyses. Results: We found a significant association of the -1072G/A (rs3776944) SNP with atopic asthma in the family-based association analysis (p = 0.0004). These results were also replicated in the case-control cohort (p = 0.009). The allele A was negatively associated with atopic asthma. We also noted a significant association in the two-locus (rs3776944G/A and rs730012A/C) haplotypic analysis of this gene both in the family-based (p = 0.03) and the case-control (p = 0.02) analyses. Conclusion: This study supports the role of the LTC4S gene polymorphism in genetic susceptibility to atopic asthma in an Indian population. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

CD14 is a lipopolysaccharide receptor known to be an important modulator of Th1-Th2 response during early childhood. Genetic association studies of theCD14gene with asthma and atopic disorders have shown positive as well as negative results in different ethnic populations. The aim of this study was to test for association of C-159T functional promoter polymorphism with atopic asthma and serum IgE levels in northern and northwestern Indian populations. DNA was assayed for theCD14C-159T polymorphism in a case-control study involving atopic asthmatics (n=187) and healthy normal controls (n=227), and in a family-based association study of 106 trios. The case-control study showed an association at the genotypic (P=0.0146) as well as the allelic level (P=0.0048). Moreover, we observed a deviation of allelic transmission from random proportions (P=0.024) in the transmission disequilibrium test analysis. When we analyzed our results for serum total IgE levels, against this polymorphism, we observed a difference at the genotypic (P=0.0026) as well as at the allelic level (P=0.0016) in a case-control study, whereas no association in the quantitative transmission disequilibrium test analysis was obtained. These findings provide suggestive evidence of association of theCD14gene locus with atopic asthma in northern and northwestern Indian populations. [ABSTRACT FROM AUTHOR]