Functional haplotypes in the PTGDR gene fail to associate with asthma in two Australian populations.
Jamrozik EF., Warrington N., McClenaghan J., Hui J., Musk AW., James A., Beilby JP., Hansen J., DE Klerk NH., Palmer LJ.
BACKGROUND AND OBJECTIVE: Haplotypes in the promoter region of the prostanoid DP receptor (PTGDR) gene have been shown to functionally influence gene transcription and to be associated with asthma in two previous case-control studies in Caucasians. This study tested the association of PTGDR haplotypes with asthma phenotypes in two large Caucasian-Australian populations. These results were incorporated in a meta-analysis with previously published data to determine the overall role for these haplotypes in the risk of asthma. METHODS: Three PTGDR promoter-region single nucleotide polymorphisms (SNP) were genotyped in 368 individuals from the Western Australian Twin Child Health study and 2988 individuals from the Busselton Health Study. Logistic regression and transition disequilibrium tests were used to assess whether SNP genotypes and three SNP haplotypes were associated with doctor-diagnosed asthma or intermediate quantitative traits. Longitudinal data from the Busselton Health Study were used to examine whether PTGDR influences changes in lung function over time. Meta-analysis incorporated the findings of this study with those of two previous studies in Caucasian populations. RESULTS: Cross-sectional associations between PTGDR haplotypes and asthma phenotypes were non-significant (P > 0.05) in both populations. Longitudinal analyses of PTGDR and lung function were also non-significant. Meta-analysis, however, suggested that haplotype TCT was significantly associated with decreased risk of asthma (OR = 0.76; P = 0.02) while haplotype CCC was not significantly associated with asthma (OR = 1.30; P = 0.07). CONCLUSIONS: These results suggest that despite the non-significant findings in the present study populations, PTGDR promoter haplotypes may account for a small but significant proportion of the risk of asthma in Caucasian populations.