Association between candidate genes and spirometric variables in Chinese

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Conference Proceeding

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Background: Asthma is caused by complex interactions between multiple susceptibility genes and environmental factors. Three genes (ARG1, ADRB2 and CRHR2) were reported to be associated with bronchodilator response in Caucasians, whereas NOS1 and NOS3 were important components of the arginase 1 pathway. GSDM1 and TOP2A, located on chromosome 17q21 as a reproducible locus identified by asthma genome-wide association study in other ethnic groups, were also candidate genes for asthma and atopy in our Chinese children. This study investigated the associations between spirometric variables and single-nucleotide polymorphisms (SNPs) of these seven candidate genes.

Methods: This study recruited both children (312 cases and 70 controls; aged 6-17 years) and adults (345 cases and 652 controls; aged ≥ 18 years). Spirometry was performed before and 30 minutes following salbutamol inhalation. Their forced expiratory volume in 1-second (FEV1) and forced vital capacity (FVC) were then measured. Thirteen SNPs of ARG1, ADRB2, CRHR2, NOS1, NOS3, GSDM1 and TOP2A were genotyped by TaqMan SNP genotyping assays using ABI Prism 7900HT thermocycler, and their associations with spirometric variables in our subjects were analyzed by multivariate linear regression.

Results: All SNPs followed Hardy-Weinberg equilibrium. In our adults, the minor allele of rs3756780 on ARG1 was associated with an additive protective effect against asthma (odds ratio 0.71, 95% confidence interval 0.54-0.93; P=0.013). Multivariate linear regression revealed FEV1 to be associated with SNPs of ARG1, CRHR2, GSDM1 and TOP2A (P=0.002-0.044), whereas FEV1/FVC was associated with SNPs of ARG1 and TOP2A (P=0.021-0.050). No significant association was found between spirometric variables and ADRB2. Among our children, FEV1 reversibility was associated with rs1003929 of CRHR2 and rs1007654 of GSDM1 (P=0.014 and 0.004, respectively).

Conclusions: This study identifies discrepant genetic associations for spirometric parameters between Chinese adults and children. Both CRHR2 and GSDM1 are associated with FEV1 in adults and FEV1 reversibility in children, whereas ARG1 and TOP2A are associated with FEV1 and FEV1/FVC only in adults. These findings highlight the importance of these candidate genes in modulating airflow limitation. None of ADRB2, NOS1 or NOS3 is a major gene for spirometric variables in the Chinese population.

Source Publication

The 9th International Congress on Pediatric Pulmonology (CIPP IX), 2010 Jun 19-21, Vienna, Austria

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