Association of prostaglandin-endoperoxide synthase 2 gene polymorphisms with asthma and atopy in Chinese children

BACKGROUND: Cyclooxygenase-2 (COX-2) plays essential roles in inflammation. Previous studies have suggested associations between prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms and prostaglandins production in asthma. OBJECTIVE: We have investigated the effects of Chinese tagging single nucleotide polymorphisms (SNPs) of PTGS2 on asthma traits in 299 Chinese asthmatic children and 175 controls. METHODS: Plasma total and allergen-specific IgE were measured by enzyme immunoassay. PTGS2.8473T-->C in the 3'-untranslated region of exon 10 and three tag SNPs covering most of the variations in PTGS2 haplotypes in Chinese were genotyped by restriction fragment length polymorphism. RESULTS: Among the four SNPs, only PTGS2.8473 showed significant association with asthma (P = 0.034) and atopy (P = 0.005 when compared with non-atopic controls; P = 0.023 with all controls). Carriers of the C allele had a 1.5-fold (95% confidence interval: 1.01-2.30) risk of developing asthma than those homozygous for the T allele. Multivariate regression revealed significant correlations between PTGS2.8473 and forced expiratory volume in 1 s (FEV(1); P = 0.002) and peak expiratory flow rate (PEFR; P = 0.001) with age and gender adjusted. Patients with the C allele of PTGS2.8473 had significantly lower FEV(1) (median: 90.0%vs 98.0%; P = 0.0047) and PEFR (70.0%vs 73.5%; P = 0.0065) than those homozygous for the T allele. No significant association between plasma total and allergen-specific IgE and these SNPs or with their haplotypes was found. CONCLUSIONS: PTGS2.8473 polymorphism is associated with asthma, atopy and lung function but not plasma IgE in Chinese children. This may help to explore the pharmacogenetics of COX-2 inhibitors.