A_16_C haplotype in the FcεRIβ gene confers a higher risk for atopic asthma in the Indian population

Sharma, Shilpy; Nagarkatti, Rana; B-Rao, Chandrika; Niphadkar, PV; Vk, Vijayan; Sharma, SK; Ghosh, Balaram

doi:10.1111/j.1399-0004.2004.00333.x

Cited by 16 publications

(18 citation statements)

References 33 publications

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“…Our earlier studies in the Indian population identified risk and protective haplotypes in the MS4A2 gene, which were associated with differential histamine release profiles and β-subunit transcript levels [12, 13]. As the earlier study [13] provided evidence for the transcriptional regulation of the gene, we focused on the promoter region in addition to the polymorphisms shown to be associated with atopic asthma in the Indian population [12].…”

Section: Discussionmentioning

confidence: 99%

“…As the earlier study [13] provided evidence for the transcriptional regulation of the gene, we focused on the promoter region in addition to the polymorphisms shown to be associated with atopic asthma in the Indian population [12]. …”

Section: Discussionmentioning

confidence: 99%

“…These samples were subsequently electrophoresed using the ABI Prism 3100 Genetic Analyzer (Applied Biosystems) and the results were analyzed using the ABI Prism GeneScan and Genotyper (Applied Biosystems). The intron 2 and 3′-UTR polymorphisms were assessed using Rsa I restriction endonuclease digestion, as described previously [12]. The genotyping was confirmed by sequencing genomic DNA from representative samples (n = 20) corresponding to the respective genotypes for all the loci investigated.…”

Section: Methodsmentioning

confidence: 99%

“…The genotyping for the microsatellite (CA) n repeat polymorphism in intron 5 was performed as described previously [12]. The fragment lengths were determined using the GeneMapper v. 3.5 (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

“…Our earlier study was carried out in 2 cohorts, 1 each from the northern and western Indian populations, and it identified 2 major haplotypes, A_16_C and G_18_T [INT2_(CA) n _3′UTR], to be positively and negatively associated with asthma, respectively [12]. Furthermore, the risk haplotype A_16_C was associated with increased histamine release (IgE receptor mediated) from basophils and higher β-subunit transcript levels [13].…”

Section: Introductionmentioning

confidence: 99%

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Promoter Polymorphism in the MS4A2 Gene and Asthma in the Indian Population

Sharma

Ghosh²

2009

Int Arch Allergy Immunol

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Background: A previous study from our laboratory identified 3-locus risk and protective haplotypes of the MS4A2 gene, a prime candidate for asthma and atopy, that were associated with differential histamine release profiles from basophils and FcεRIβ transcript levels in the Indian population. Methods: To explore the role of promoter polymorphisms in the observed association, 4 additional promoter polymorphisms (–752C/T, –654C/T, –426T/C and –109T/C) were investigated in 240 nuclear families with atopic asthma, 237 atopic asthmatics and 221 unrelated controls, all of whom were clinically well characterized. The β-subunit transcript levels were measured for 15 individuals and were correlated with the associated promoter polymorphisms. Results: We observed a significant association of the –752C/T and –109T/C polymorphisms with asthma, in addition to the already reported association for the INT2 G/A, intron 5 (CA)_n and 3′-UTR C/T polymorphisms. Additionally, the allele T of the –109T/C polymorphism was associated with a reduced risk of asthma and lower percent peripheral blood eosinophils, thereby pointing towards a protective role for this allele in asthma. Further, the 7-locus haplotypes C_C_T_C_A_16_C and T_C_T_T_G_18_T were identified as the major risk/susceptibility and protective haplotypes, respectively (p < 0.05). Three-locus sliding-window haplotype analysis also identified the –426T/C, –109T/C and INT2 G/A polymorphisms to be in regions of high priority (p < 0.00001). Indeed, the –109T allele was found to be associated with reduced expression levels for FcεRIβ. Conclusions: A promoter-dependent mechanism with altered transcriptional regulation of FcεRIβ may be involved for its association with asthma. These results, therefore, could be useful in predicting the genetic susceptibility of individuals for developing asthma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Promoter Polymorphism in the MS4A2 Gene and Asthma in the Indian Population

Sharma

Ghosh²

2009

Int Arch Allergy Immunol

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The Indian Genome Variation database (IGVdb): a project overview

2005

Hum Genet

132

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Indian population, comprising of more than a billion people, consists of 4693 communities with several thousands of endogamous groups, 325 functioning languages and 25 scripts. To address the questions related to ethnic diversity, migrations, founder populations, predisposition to complex disorders or pharmacogenomics, one needs to understand the diversity and relatedness at the genetic level in such a diverse population. In this backdrop, six constituent laboratories of the Council of Scientific and Industrial Research (CSIR), with funding from the Government of India, initiated a network program on predictive medicine using repeats and single nucleotide polymorphisms. The Indian Genome Variation (IGV) consortium aims to provide data on validated SNPs and repeats, both novel and reported, along with gene duplications, in over a thousand genes, in 15,000 individuals drawn from Indian subpopulations. These genes have been selected on the basis of their relevance as functional and positional candidates in many common diseases including genes relevant to pharmacogenomics. This is the first large-scale comprehensive study of the structure of the Indian population with wide-reaching implications. A comprehensive platform for Indian Genome Variation (IGV) data management, analysis and creation of IGVdb portal has also been developed. The samples are being collected following ethical guidelines of Indian Council of Medical Research (ICMR) and Department of Biotechnology (DBT), India. This paper reveals the structure of the IGV project highlighting its various aspects like genesis, objectives, strategies for selection of genes, identification of the Indian subpopulations, collection of samples and discovery and validation of genetic markers, data analysis and monitoring as well as the project's data release policy.

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Association of an intragenic microsatellite marker in the CC16 gene with asthma in the Indian population

Sharma

Ghosh

2004

J Hum Genet

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The gene for Clara cell secretory protein (CC16) is an ideal candidate for investigating genetic predisposition to asthma because of its role in the airway as an antiinflammatory molecule, differences in its levels between asthmatics and healthy controls, and its genetic location (11q13). We investigated the association of an SNP (A38G) and an intragenic repeat polymorphism in the CC16 gene with asthma and its associated traits, such as total serum IgE levels, in a case control as well as in a family based study design. A significant association was observed for the microsatellite repeat at the level of alleles and genotypes with asthma (P<0.05) in both the study designs. However, no association was observed for the A38G SNP with asthma. When haplotypes were constructed for these two loci and compared, the haplotype A_18 was found at higher frequency in patients (OR=1.59, 95%CI=1.08, 2.33, P=0.016). Also, in the family based design, a biased transmission was observed for haplotypes from parents to affected offspring (P=0.003). Individually, haplotype A_18 showed preferential transmission (82.6%) to affected offspring (P=0.001), thereby confirming the case-control results. In summary, this is the first study identifying the CC16 gene to be associated with asthma in the Indian population.

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A_16_C haplotype in the FcεRIβ gene confers a higher risk for atopic asthma in the Indian population

Cited by 16 publications

References 33 publications

Promoter Polymorphism in the <i>MS4A2</i> Gene and Asthma in the Indian Population

Promoter Polymorphism in the <i>MS4A2</i> Gene and Asthma in the Indian Population

The Indian Genome Variation database (IGVdb): a project overview

Association of an intragenic microsatellite marker in the CC16 gene with asthma in the Indian population

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