IngentaConnect Interleukin-10 promoter polymorphisms and atopic asthma in North ...

Abstract:

Summary Background

IL-10 is an anti-inflammatory cytokine primarily produced by monocytes and macrophages and plays a key role in asthma. IL10 gene, present in chromosome 1q31–q32, is regulated primarily by transcription and its expression is found to be lower in asthmatics. Earlier studies in diverse populations have identified several promoter polymorphisms. However, no study has been carried out in a genetically untapped large population from the Indian Subcontinent. Objective

To investigate the association of the IL10 promoter polymorphisms and asthma in the North Indian population. Methods

The association study was conducted in a case–control as well as in a family-based design. Polymorphism at −1082 A/G, −819 C/T and −592 C/A nucleotides were genotyped in ethnically matched unrelated patients (N=272), unrelated controls (N=307) and nuclear families (N=164). Results

A suggestive evidence of association was obtained for −1082 A/G polymorphism at the level of alleles and genotypes with asthma in the case–control study (P=0.03). A three-locus haplotype (ATA) was found to be more in asthmatics than in control individuals (P=0.0085). On the other hand, a novel haplotype ATC was found to be more in controls than in asthmatics (P=0.012). These results were further tested in a family-based study. A deviation of transmission was observed for the −1082 A/G polymorphism (P=0.003). The ATA haplotype showed a preferential transmission in asthmatics (P=0.03), while the GCC and a novel ATC haplotype showed preferential non-transmission in asthmatic individuals (P=0.03 and 0.001, respectively). Conclusions

Using both case–control and family studies, we provide suggestive evidence that the ATA haplotype is positively, whereas GCC and a novel ATC haplotypes of IL10 gene are negatively associated with asthma in Indian population. Our results are interesting enough as to intensify further research to elucidate the functional significance of these single-nucleotide polymorphisms and haplotypes in asthma pathogenesis.

Keywords: asthma; haplotypes; IL10; North Indian population

Document Type: Research article

DOI: 10.1111/j.1365-2222.2005.02273.x

Affiliations: 1: Institute of Genomics and Integrative Biology, Mall Road, Delhi, India and 2: Asthma and Allergy Centre, Mumbai, India

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Interleukin-10 promoter polymorphisms and atopic asthma in North Indians