BACKGROUND: Single-nucleotide polymorphism (SNP)-based genome-wide association study revealed that markers on chromosome 17q21 were linked to childhood asthma but not atopy in Caucasians, with the strongest signal being detected for the SNP rs7216389 in the ORMDL3 gene. Such association was unknown in Chinese. This study delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21, and investigated the relationship between these SNPs and asthma and plasma IgE in southern Chinese children. METHODS: Asthmatic children and non-allergic controls were recruited from pediatric clinics. Their plasma total and aeroallergen-specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21 region were genotyped by multiplex SNaPshot, and their genotype associations with asthma traits analyzed using multivariate regression. RESULTS: 315 patients and 192 controls were enrolled. The allele frequency for C allele of rs7216389 varied significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs including rs7216389 (P = 0.019-0.034), whereas atopy was associated only with rs11650680 (P = 0.0004). Linear regression revealed the covariates for plasma total IgE to be significant for rs11650680 (P = 0.008-0.0002). Haplotypic associations were found with atopy and increased plasma total IgE, with the respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be 0.21 and 0.09-0.52 (P = 0.0002) and 0.41 and 0.18-0.90 (P = 0.025). CONCLUSION: Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but such association may involve genes other than ORMDL3 in this region.
BACKGROUND: Single-nucleotide polymorphism (SNP)-based genome-wide association study revealed that markers on chromosome 17q21 were linked to childhood asthma but not atopy in Caucasians, with the strongest signal being detected for the SNP rs7216389 in the ORMDL3 gene. Such association was unknown in Chinese. This study delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21, and investigated the relationship between these SNPs and asthma and plasma IgE in southern Chinese children. METHODS: Asthmatic children and non-allergic controls were recruited from pediatric clinics. Their plasma total and aeroallergen-specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21 region were genotyped by multiplex SNaPshot, and their genotype associations with asthma traits analyzed using multivariate regression. RESULTS: 315 patients and 192 controls were enrolled. The allele frequency for C allele of rs7216389 varied significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs including rs7216389 (P = 0.019-0.034), whereas atopy was associated only with rs11650680 (P = 0.0004). Linear regression revealed the covariates for plasma total IgE to be significant for rs11650680 (P = 0.008-0.0002). Haplotypic associations were found with atopy and increased plasma total IgE, with the respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be 0.21 and 0.09-0.52 (P = 0.0002) and 0.41 and 0.18-0.90 (P = 0.025). CONCLUSION: Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but such association may involve genes other than ORMDL3 in this region.
Authors: Sara E Dobbins; Fay J Hosking; Sanjay Shete; Georgina Armstrong; Anthony Swerdlow; Yanhong Liu; Robert Yu; Ching Lau; Minouk J Schoemaker; Sarah J Hepworth; Kenneth Muir; Melissa Bondy; Richard S Houlston Journal: Int J Cancer Date: 2010-05-25 Impact factor: 7.396
Authors: Berta Almoguera; Lyam Vazquez; Frank Mentch; John Connolly; Jennifer A Pacheco; Agnes S Sundaresan; Peggy L Peissig; James G Linneman; Catherine A McCarty; David Crosslin; David S Carrell; Todd Lingren; Bahram Namjou-Khales; John B Harley; Eric Larson; Gail P Jarvik; Murray Brilliant; Marc S Williams; Iftikhar J Kullo; Erik B Hysinger; Patrick M A Sleiman; Hakon Hakonarson Journal: Am J Respir Crit Care Med Date: 2017-02-15 Impact factor: 21.405