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.
Chan
I H S
IH
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Tang
N L S
NL
Leung
T F
TF
Ma
S L
SL
Zhang
Y P
YP
Wong
G W K
GW
Wong
C K
CK
Lam
C W K
CW
D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood; D008565:Membrane Proteins / Q000235:genetics*; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012129:Respiratory Function Tests
D008565:Membrane Proteins; D007073:Immunoglobulin E; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human