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Published ahead of print on April 22, 2004, doi:10.1165/rcmb.2003-0128OC

Am. J. Respir. Cell Mol. Biol., Volume 31, Number 3, September 2004, 317-321

A more recent version of this article appeared on September 1, 2004
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Submitted on April 10, 2003
Revised on April 22, 2004

Signal Transducer and Activator of Transcription 6 haplotypes and asthma in the Indian population

Rana Nagarkatti1, Chandrika B-Rao1, Vannankandi Vijayan2, Surendra K Sharma3, and Balaram Ghosh1*

1 Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi, Delhi, India, 2 Department of Medicine, Vallabhbhai Patel Chest Institute, Delhi, Delhi, India, 3 Department of Medicine, All India Institute of Medical Sciences, Delhi, Delhi, India

* To whom correspondence should be addressed. E-mail: bghosh{at}igib.res.in,bghosh_igib@yahoo.com.

In this paper, we report for the first time, the results of an investigation on the association of Signal Transducer and Activator of Transcription-6 (STAT6) with asthma in the Indian population. A novel polymorphic CA-repeat in the proximal promoter region [R1] and a previously identified CA-repeat in the 5'-UTR [R3] were genotyped, and haplotypes [R1_R3] were generated using PHASE. The 16 repeat allele at the R1 locus was positively associated (p=0.01) with asthma. The 15 and 16 repeat alleles at the R3 locus were positively (p<10-4) and negatively (p<10-5) associated with asthma, respectively. Further, the 17_15 (p=0.0031) and 16_15 (p=0.001) haplotype were found to be positively associated with asthma whereas 17_14, 24_16 and 23_16 were negatively associated (p<10-5). It appears that the R3 and R1 loci together play a bigger role in asthma than either of them alone, and the R3 locus has a larger effect than the R1 locus. Although alleles at the R1 locus appeared to be associated with total serum IgE level, the genotypes showed no association, and the R3 locus showed no effect. As no exonic variants of STAT6 are known as yet, repeat polymorphisms in the regulatory regions and their haplotypes could be important in deciphering the genetic role of STAT6 in asthma and atopy.




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