Qiurong Fang1, Hailing Zhao, Aihua Wang, Yaoqin Gong, Qiji Liu. 1. Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
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.
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 asthmapatients 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.
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