The prostanoid DP receptor (PTGDR) is shown to be involved in the asthma patho-physiology and the results from the published genetic association studies are inconsistent. Four single nucleotide polymorphisms (SNPs) in PTGDR were genotyped in 342 and 294 families from UK and Denmark respectively. Asthma and asthma-related phenotypes were analyzed using family-based association analyses. In the UK families, a promoter polymorphism (-731A/G) showed significant associations with asthma (P=0.0022), atopic asthma (P=0.0044), bronchial hyperreactivity or BHR (P=0.00120) and strict asthma (P=0.0008). The P-values for asthma, BHR and strict asthma were significant even after the most stringent correction for the number of markers and the number of phenotypes analyzed (<0.0031). An intronic polymorphism (+6651C/T) also showed significant associations with asthma (P=0.0302), atopic asthma (P=0.0131), BHR (P=0.0249) and strict asthma (P=0.0261). In the Danish families, an intronic polymorphism (+6541C/T) showed significant associations with asthma (P=0.0071), atopic asthma (P=0.0348), BHR (P=0.0033) and strict asthma (P=0.0381). The results of haplotype analyses supported the ones of the single SNP analyses. Thus, we demonstrated significant evidence of association between polymorphisms in PTGDR with asthma phenotypes in the two Caucasian populations.