Abstract

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. 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. 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. 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. 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.

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