BACKGROUND: In view of the hygiene hypothesis and the involvement of acidic mammalian chitinase (CHIA) in the effector responses of IL-13 with asthma, CHIA (GeneID-27159) is a potential asthma candidate gene. OBJECTIVE: To investigate the association of CHIA polymorphisms with atopic asthma and serum total IgE levels. METHODS: Twenty-one single nucleotide polymorphisms were identified by sequencing DNA of 60 individuals. On the basis of linkage disequilibrium, 6 polymorphisms were selected and genotyped in unrelated atopic patients with asthma (N = 270) and controls (N = 292) and an independent pediatric cohort (patients, 150; controls, 101). Electrophoretic mobility shift assay and reporter gene assays were also performed. RESULTS: The rs3806448G/A promoter polymorphism showed significant association with atopic asthma (P(adult) = .00001 and P(pediatric) = .0002) and serum total IgE (P < .05). Also rs2282290G/A was associated with atopic asthma (P(adult) = .00009 and P(pediatric) = .00003), whereas the rs10494132C/T polymorphism was associated with serum total IgE in the patients (P < .05). We also showed that the promoter single nucleotide polymorphisms altered the transcriptional activity of CHIA promoter and the C to T substitution at rs10494132 abrogated the Octamer transcription factor-1 (Oct-1) binding site. CONCLUSION: Our results establish a significant association of CHIA with atopic asthma and serum total IgE levels in the Indian population.
BACKGROUND: In view of the hygiene hypothesis and the involvement of acidic mammalian chitinase (CHIA) in the effector responses of IL-13 with asthma, CHIA (GeneID-27159) is a potential asthma candidate gene. OBJECTIVE: To investigate the association of CHIA polymorphisms with atopic asthma and serum total IgE levels. METHODS: Twenty-one single nucleotide polymorphisms were identified by sequencing DNA of 60 individuals. On the basis of linkage disequilibrium, 6 polymorphisms were selected and genotyped in unrelated atopicpatients with asthma (N = 270) and controls (N = 292) and an independent pediatric cohort (patients, 150; controls, 101). Electrophoretic mobility shift assay and reporter gene assays were also performed. RESULTS: The rs3806448G/A promoter polymorphism showed significant association with atopic asthma (P(adult) = .00001 and P(pediatric) = .0002) and serum total IgE (P < .05). Also rs2282290G/A was associated with atopic asthma (P(adult) = .00009 and P(pediatric) = .00003), whereas the rs10494132C/T polymorphism was associated with serum total IgE in the patients (P < .05). We also showed that the promoter single nucleotide polymorphisms altered the transcriptional activity of CHIA promoter and the C to T substitution at rs10494132 abrogated the Octamer transcription factor-1 (Oct-1) binding site. CONCLUSION: Our results establish a significant association of CHIA with atopic asthma and serum total IgE levels in the Indian population.
Authors: Ann Chen Wu; Jessica Lasky-Su; Christine A Rogers; Barbara J Klanderman; Augusto A Litonjua Journal: Am J Respir Crit Care Med Date: 2010-06-10 Impact factor: 21.405
Authors: Steven J Van Dyken; Daniel Garcia; Paul Porter; Xiaozhu Huang; Patricia J Quinlan; Paul D Blanc; David B Corry; Richard M Locksley Journal: J Immunol Date: 2011-08-08 Impact factor: 5.422
Authors: Chun Geun Lee; Carla A Da Silva; Charles S Dela Cruz; Farida Ahangari; Bing Ma; Min-Jong Kang; Chuan-Hua He; Seyedtaghi Takyar; Jack A Elias Journal: Annu Rev Physiol Date: 2011 Impact factor: 19.318
Authors: Alan P Knutsen; Hari M Vijay; Barbara Kariuki; Luis A Santiago; Ralph Graff; Jonathan D Wofford; Maulik R Shah Journal: Clin Mol Allergy Date: 2010-03-18
Authors: Max A Seibold; Tiffany A Reese; Shweta Choudhry; Muhammad T Salam; Kenny Beckman; Celeste Eng; Amha Atakilit; Kelley Meade; Michael Lenoir; H Geoffrey Watson; Shannon Thyne; Rajesh Kumar; Kevin B Weiss; Leslie C Grammer; Pedro Avila; Robert P Schleimer; John V Fahy; Jose Rodriguez-Santana; William Rodriguez-Cintron; Rolf G Boot; Dean Sheppard; Frank D Gilliland; Richard M Locksley; Esteban G Burchard Journal: J Biol Chem Date: 2009-05-12 Impact factor: 5.157