Objectives: Eotaxin (CCL11) is a small protein, produced in the lungs of asthmatic patients and is a potent chemo attractant for eosinophils. We sought to elucidate the role of eotaxin in asthma by an association study of functional and novel eotaxin polymorphisms in case-control and family-based study designs. Methods: Eotaxin +67G/A, -384A/G and -426C/T SNPs and a hexanucleotide (GAAGGA)n repeat 10.9kb upstream of the gene were genotyped in a cohort of age, sex and ethnically matched asthmatics (N=235) and normal control (N=239), and also in a study population of 230 asthmatic families recruited from the North/North-West India. Serum total IgE (TsIgE) and plasma eotaxin levels were measured using ELISA. Results: +67G/A polymorphism was found to be significantly associated with asthma in case-control (p=0.0086) as well as family-based studies (p=0.0058). We also demonstrated its functional role, as it was correlated with plasma eotaxin levels (p=0.006). Further, -384C/T SNP was found to be significantly associated with log10TsIgE (p=0.016 in case-control and p=0.018 in families) as well as eotaxin levels (p=0.007). Most interestingly, we observed for the first time a highly significant association of the newly studied (GAAGGA)n hexanucleotide repeat with asthma (p=3x10-6), log10TsIgE (p=0.0058) and eotaxin levels (p=0.004). We also identified G_A_C_8 as an important risk haplotype associated with high TsIgE and plasma eotaxin levels. Conclusions: This study provides further evidence that eotaxin polymorphisms are associated with the development of asthma by regulating eotaxin levels and reinforce towards the scanning of other chemokine genes present at 17q21 locus for their association with asthma and related phenotypes.
- Indian population
- Repeat polymorphism
- eotaxin level
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