Genetic variants of 17q21 are associated with childhood‐onset asthma and related phenotypes in a northeastern Han Chinese population: a case–control study

Abstract

A genome-wide association study (GWAS) suggested that variants on chromosome 17q21 were associated with childhood-onset asthma in white populations. Two replication studies had been conducted in southern Han Chinese population in 2009 and 2012. However, these two Chinese replication results were inconsistent. To further confirm the role of 17q21 common variants, an association study of 17q21 single nucleotide polymorphisms (SNPs) with the risk of childhood-onset asthma was performed in a Han population from northeastern China. In this study, rs3894194, rs12603332 and rs11650680 were genotyped in 435 asthmatic children and 601 healthy controls by using a SNaPshot method. Our data showed that the allelic frequency of rs12603332 and rs11650680 showed significant differences between asthmatic cases and healthy controls, with an odds ratio (OR) of 1.36 [95% confidence interval (CI) 1.12-1.65, P=0.002] and an OR of 1.36 (95% CI 1.07-1.74, P=0.01). Genotype distribution analysis also showed the significant associations of the above two loci with childhood asthma under dominant, recessive and additive model (dominant OR=1.57, 95% CI 1.04-2.36, P=0.032; recessive OR=1.41, 95% CI 1.09-1.83, P=0.009; additive OR=1.97, 95% CI 1.24-3.14, P=0.004; recessive OR=1.50, 95% CI 1.13-1.98, P=0.005). Besides, linear regression analysis showed that rs3894194 and rs12603332 were also significantly associated with asthma phenotypes such as log10 -transformed immunoglobulin E (IgE) level (IU/ml) and log10 -transformed eosinophil percentage (dominant, P=0.04; additive, P=0.01; recessive, P=0.04; recessive, P=0.03; additive, P=0.02). Collectively, our findings suggest that orosomucoid 1-like 3 (ORMDL3) locus on chromosome 17q21 is a risk factor for childhood-onset asthma in northeastern Han Chinese population. Further studies will be needed to elucidate the pathogenesis that ORMDL3 locus predisposes to childhood-onset asthma.

The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma

“…To deal with this problem, another study on Chinese eastern Han population was conducted in 2014. The data confirmed that a SNP in the ORMDL3 locus on chromosome 17q21 is a risk factor for childhood-onset asthma (37). Conflicting results also appeared about the association of 17q12-21 polymorphisms with increased IgE levels in asthma patients.…”

Pediatric allergy and immunology in China

“…It is now clear that the manifestations of allergic disorders are the results of complex interactions between genetic and environmental factors. Using both the candidate gene and the genomewide association approaches, many studies of genetics susceptibilities for allergic disorders in Chinese have been performed . As exemplified by studies of asthma genetic studies, there are substantial differences in the frequencies of single nucleotide polymorphisms (SNPs) and haplotype blocks for asthma genes in Chinese and other populations .…”

“…Using both the candidate gene and the genomewide association approaches, many studies of genetics susceptibilities for allergic disorders in Chinese have been performed. [28][29][30][31][32] As exemplified by studies of asthma genetic studies, there are substantial differences in the frequencies of single nucleotide polymorphisms (SNPs) and haplotype blocks for asthma genes in Chinese and other populations. 33 As demonstrated by the complexity of the interaction between polymorphisms of the CD14 gene and exposures to microbes on the risk of asthma, 34 future international collaborative efforts with simultaneous assessment of relevant environmental exposures are needed to clearly understand the contribution of various susceptibility genes in the pathogenesis of allergic disorders in different ethnic groups.…”

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

“…In 2007, orosomucoid-like 3 (ORMDL3) was first reported to be associated with bronchial asthma and was subsequently replicated in various ethnic populations (13)(14)(15)(16)(17). Then several groups showed the association of ORMDL3 with type 1 diabetes (18), inflammatory bowel diseases (19), ankylosing spondylitis (20,21), and atherosclerosis (22).…”