Skip to main content
Top
Published in: BMC Medical Genetics 1/2011

Open Access 01-12-2011 | Research article

Association of genetic variants in chromosome 17q21 and adult-onset asthma in a Chinese Han population

Authors: Rongfang Qiu, Hailing Zhao, Aihua Wang, Yaoqin Gong, Qiji Liu

Published in: BMC Medical Genetics | Issue 1/2011

Login to get access

Abstract

Background

Genome-wide association studies of asthma have identified a novel region containing ORMDL3 at chromosome 17q21 that is strongly associated with childhood-onset asthma and significantly linked to ORMDL3 transcript abundance. These results have been successfully replicated in childhood-onset asthma cohorts in several ethnic groups. In this study, we aimed to evaluate the association of polymorphisms in ORMDL3, GSDMB, ZPBP2 and IKZF3 and adult-onset asthma in a Chinese Han population.

Methods

We genotyped 5 single nucleotide polymorphisms (SNPs) at chromosome 17q21 in 1,366 Han Chinese people comprising 710 patients with adult-onset asthma and 656 healthy controls. We compared the 2 groups in terms of allele and haplotype frequencies. Transcript levels were measured in leukocytes from 61 asthma patients by quantitative real-time PCR.

Results

We found the 5 SNPs significantly associated with asthma (P<0.05), of which 2, rs11557467 and rs9303277, were strongly associated (P<0.001). Subjects carrying the G allele of rs11557467 or the C allele of rs9303277 showed increased risk of asthma (odds ratio [OR] 1.27, 95% confidence interval 1.07-1.51, P = 0.006, and OR 1.27, 1.07-1.49, P = 0.005, respectively), even after adjusting for age and sex. The risk of asthma was lower for carriers of the haplotype CTGTT (OR 0.81, 0.67-0.97, P = 0.02). The risk allele for each SNP was associated with increased expression of ORMDL3 and GSDMB in leukocytes (all p<0.05).

Conclusions

Our replication study suggests that variants in 17q21 are significantly associated with risk of adult-onset asthma and gene expression in a Chinese Han population.
Appendix
Available only for authorised users
Literature
1.
go back to reference Chae SC, Li CS, Kim KM, Yang JY, Zhang Q, Lee YC, Yang YS, Chung HT: Identification of polymorphisms in human interleukin-27 and their association with asthma in a Korean population. J Hum Genet. 2007, 52 (4): 355-361. 10.1007/s10038-007-0123-8.CrossRefPubMed Chae SC, Li CS, Kim KM, Yang JY, Zhang Q, Lee YC, Yang YS, Chung HT: Identification of polymorphisms in human interleukin-27 and their association with asthma in a Korean population. J Hum Genet. 2007, 52 (4): 355-361. 10.1007/s10038-007-0123-8.CrossRefPubMed
2.
go back to reference Cookson W: Genetics and genomics of asthma and allergic diseases. Immunol Rev. 2002, 190: 195-206. 10.1034/j.1600-065X.2002.19015.x.CrossRefPubMed Cookson W: Genetics and genomics of asthma and allergic diseases. Immunol Rev. 2002, 190: 195-206. 10.1034/j.1600-065X.2002.19015.x.CrossRefPubMed
3.
go back to reference Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, Depner M, von Berg A, Bufe A, Rietschel E, et al: Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007, 448 (7152): 470-473. 10.1038/nature06014.CrossRefPubMed Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, Depner M, von Berg A, Bufe A, Rietschel E, et al: Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007, 448 (7152): 470-473. 10.1038/nature06014.CrossRefPubMed
4.
go back to reference Hjelmqvist L, Tuson M, Marfany G, Herrero E, Balcells S, Gonzalez-Duarte R: ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins. Genome Biol. 2002, 3 (6): RESEARCH0027.-CrossRefPubMedPubMedCentral Hjelmqvist L, Tuson M, Marfany G, Herrero E, Balcells S, Gonzalez-Duarte R: ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins. Genome Biol. 2002, 3 (6): RESEARCH0027.-CrossRefPubMedPubMedCentral
5.
go back to reference Breslow DK, Collins SR, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, Ejsing CS, Weissman JS: Orm family proteins mediate sphingolipid homeostasis. Nature. 463 (7284): 1048-1053. Breslow DK, Collins SR, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, Ejsing CS, Weissman JS: Orm family proteins mediate sphingolipid homeostasis. Nature. 463 (7284): 1048-1053.
6.
go back to reference Carl-McGrath S, Schneider-Stock R, Ebert M, Rocken C: Differential expression and localisation of gasdermin-like (GSDML), a novel member of the cancer-associated GSDMDC protein family, in neoplastic and non-neoplastic gastric, hepatic, and colon tissues. Pathology. 2008, 40 (1): 13-24. 10.1080/00313020701716250.CrossRefPubMed Carl-McGrath S, Schneider-Stock R, Ebert M, Rocken C: Differential expression and localisation of gasdermin-like (GSDML), a novel member of the cancer-associated GSDMDC protein family, in neoplastic and non-neoplastic gastric, hepatic, and colon tissues. Pathology. 2008, 40 (1): 13-24. 10.1080/00313020701716250.CrossRefPubMed
7.
go back to reference Tavendale R, Macgregor DF, Mukhopadhyay S, Palmer CN: A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications. J Allergy Clin Immunol. 2008, 121 (4): 860-863. 10.1016/j.jaci.2008.01.015.CrossRefPubMed Tavendale R, Macgregor DF, Mukhopadhyay S, Palmer CN: A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications. J Allergy Clin Immunol. 2008, 121 (4): 860-863. 10.1016/j.jaci.2008.01.015.CrossRefPubMed
8.
go back to reference Bouzigon E, Corda E, Aschard H, Dizier MH, Boland A, Bousquet J, Chateigner N, Gormand F, Just J, Le Moual N, et al: Effect of 17q21 variants and smoking exposure in early-onset asthma. N Engl J Med. 2008, 359 (19): 1985-1994. 10.1056/NEJMoa0806604.CrossRefPubMed Bouzigon E, Corda E, Aschard H, Dizier MH, Boland A, Bousquet J, Chateigner N, Gormand F, Just J, Le Moual N, et al: Effect of 17q21 variants and smoking exposure in early-onset asthma. N Engl J Med. 2008, 359 (19): 1985-1994. 10.1056/NEJMoa0806604.CrossRefPubMed
9.
go back to reference Madore AM, Tremblay K, Hudson TJ, Laprise C: Replication of an association between 17q21 SNPs and asthma in a French-Canadian familial collection. Hum Genet. 2008, 123 (1): 93-95. 10.1007/s00439-007-0444-x.CrossRefPubMed Madore AM, Tremblay K, Hudson TJ, Laprise C: Replication of an association between 17q21 SNPs and asthma in a French-Canadian familial collection. Hum Genet. 2008, 123 (1): 93-95. 10.1007/s00439-007-0444-x.CrossRefPubMed
10.
go back to reference Sleiman PM, Annaiah K, Imielinski M, Bradfield JP, Kim CE, Frackelton EC, Glessner JT, Eckert AW, Otieno FG, Santa E, et al: ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry. J Allergy Clin Immunol. 2008, 122 (6): 1225-1227. 10.1016/j.jaci.2008.06.041.CrossRefPubMed Sleiman PM, Annaiah K, Imielinski M, Bradfield JP, Kim CE, Frackelton EC, Glessner JT, Eckert AW, Otieno FG, Santa E, et al: ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry. J Allergy Clin Immunol. 2008, 122 (6): 1225-1227. 10.1016/j.jaci.2008.06.041.CrossRefPubMed
11.
go back to reference Wu H, Romieu I, Sienra-Monge JJ, Li H, del Rio-Navarro BE, London SJ: Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma. Allergy. 2009, 64 (4): 629-635. 10.1111/j.1398-9995.2008.01912.x.CrossRefPubMed Wu H, Romieu I, Sienra-Monge JJ, Li H, del Rio-Navarro BE, London SJ: Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma. Allergy. 2009, 64 (4): 629-635. 10.1111/j.1398-9995.2008.01912.x.CrossRefPubMed
12.
go back to reference Ferreira MA, McRae AF, Medland SE, Nyholt DR, Gordon SD, Wright MJ, Henders AK, Madden PA, Visscher PM, Wray NR, et al: Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia. Eur J Hum Genet. Ferreira MA, McRae AF, Medland SE, Nyholt DR, Gordon SD, Wright MJ, Henders AK, Madden PA, Visscher PM, Wray NR, et al: Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia. Eur J Hum Genet.
13.
go back to reference Galanter J, Choudhry S, Eng C, Nazario S, Rodriguez-Santana JR, Casal J, Torres-Palacios A, Salas J, Chapela R, Watson HG, et al: ORMDL3 gene is associated with asthma in three ethnically diverse populations. Am J Respir Crit Care Med. 2008, 177 (11): 1194-1200. 10.1164/rccm.200711-1644OC.CrossRefPubMedPubMedCentral Galanter J, Choudhry S, Eng C, Nazario S, Rodriguez-Santana JR, Casal J, Torres-Palacios A, Salas J, Chapela R, Watson HG, et al: ORMDL3 gene is associated with asthma in three ethnically diverse populations. Am J Respir Crit Care Med. 2008, 177 (11): 1194-1200. 10.1164/rccm.200711-1644OC.CrossRefPubMedPubMedCentral
14.
go back to reference Hirota T, Harada M, Sakashita M, Doi S, Miyatake A, Fujita K, Enomoto T, Ebisawa M, Yoshihara S, Noguchi E, et al: Genetic polymorphism regulating ORM1-like 3 (Saccharomyces cerevisiae) expression is associated with childhood atopic asthma in a Japanese population. J Allergy Clin Immunol. 2008, 121 (3): 769-770. 10.1016/j.jaci.2007.09.038.CrossRefPubMed Hirota T, Harada M, Sakashita M, Doi S, Miyatake A, Fujita K, Enomoto T, Ebisawa M, Yoshihara S, Noguchi E, et al: Genetic polymorphism regulating ORM1-like 3 (Saccharomyces cerevisiae) expression is associated with childhood atopic asthma in a Japanese population. J Allergy Clin Immunol. 2008, 121 (3): 769-770. 10.1016/j.jaci.2007.09.038.CrossRefPubMed
15.
go back to reference Leung TF, Sy HY, Ng MC, Chan IH, Wong GW, Tang NL, Waye MM, Lam CW: Asthma and atopy are associated with chromosome 17q21 markers in Chinese children. Allergy. 2009, 64 (4): 621-628. 10.1111/j.1398-9995.2008.01873.x.CrossRefPubMed Leung TF, Sy HY, Ng MC, Chan IH, Wong GW, Tang NL, Waye MM, Lam CW: Asthma and atopy are associated with chromosome 17q21 markers in Chinese children. Allergy. 2009, 64 (4): 621-628. 10.1111/j.1398-9995.2008.01873.x.CrossRefPubMed
16.
go back to reference Wang P, Liu QJ, Li JS, Li HC, Wei CH, Guo CH, Gong YQ: Lack of association between ADAM33 gene and asthma in a Chinese population. Int J Immunogenet. 2006, 33 (4): 303-306. 10.1111/j.1744-313X.2006.00617.x.CrossRefPubMed Wang P, Liu QJ, Li JS, Li HC, Wei CH, Guo CH, Gong YQ: Lack of association between ADAM33 gene and asthma in a Chinese population. Int J Immunogenet. 2006, 33 (4): 303-306. 10.1111/j.1744-313X.2006.00617.x.CrossRefPubMed
17.
go back to reference Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, et al: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007, 81 (3): 559-575. 10.1086/519795.CrossRefPubMedPubMedCentral Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, et al: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007, 81 (3): 559-575. 10.1086/519795.CrossRefPubMedPubMedCentral
18.
go back to reference Shi YY, He L: SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005, 15 (2): 97-98. 10.1038/sj.cr.7290272.CrossRefPubMed Shi YY, He L: SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005, 15 (2): 97-98. 10.1038/sj.cr.7290272.CrossRefPubMed
19.
go back to reference Laitinen T, Rasanen M, Kaprio J, Koskenvuo M, Laitinen LA: Importance of genetic factors in adolescent asthma: a population-based twin-family study. Am J Respir Crit Care Med. 1998, 157: (4 Pt 1):1073-1078.CrossRef Laitinen T, Rasanen M, Kaprio J, Koskenvuo M, Laitinen LA: Importance of genetic factors in adolescent asthma: a population-based twin-family study. Am J Respir Crit Care Med. 1998, 157: (4 Pt 1):1073-1078.CrossRef
20.
go back to reference van Beijsterveldt CE, Boomsma DI: Genetics of parentally reported asthma, eczema and rhinitis in 5-yr-old twins. Eur Respir J. 2007, 29 (3): 516-521. 10.1183/09031936.00065706.CrossRefPubMed van Beijsterveldt CE, Boomsma DI: Genetics of parentally reported asthma, eczema and rhinitis in 5-yr-old twins. Eur Respir J. 2007, 29 (3): 516-521. 10.1183/09031936.00065706.CrossRefPubMed
21.
go back to reference Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO: A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 363 (13): 1211-1221. Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO: A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 363 (13): 1211-1221.
22.
go back to reference Verlaan DJ, Berlivet S, Hunninghake GM, Madore AM, Lariviere M, Moussette S, Grundberg E, Kwan T, Ouimet M, Ge B, et al: Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease. Am J Hum Genet. 2009, 85 (3): 377-393. 10.1016/j.ajhg.2009.08.007.CrossRefPubMedPubMedCentral Verlaan DJ, Berlivet S, Hunninghake GM, Madore AM, Lariviere M, Moussette S, Grundberg E, Kwan T, Ouimet M, Ge B, et al: Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease. Am J Hum Genet. 2009, 85 (3): 377-393. 10.1016/j.ajhg.2009.08.007.CrossRefPubMedPubMedCentral
23.
go back to reference Cantero-Recasens G, Fandos C, Rubio-Moscardo F, Valverde MA, Vicente R: The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet. 19 (1): 111-121. Cantero-Recasens G, Fandos C, Rubio-Moscardo F, Valverde MA, Vicente R: The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet. 19 (1): 111-121.
Metadata
Title
Association of genetic variants in chromosome 17q21 and adult-onset asthma in a Chinese Han population
Authors
Rongfang Qiu
Hailing Zhao
Aihua Wang
Yaoqin Gong
Qiji Liu
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2011
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-12-133

Other articles of this Issue 1/2011

BMC Medical Genetics 1/2011 Go to the issue