Promoter genetic variants of prostanoid DP receptor (<i>PTGDR</i>) gene in patients with asthma

Sanz, Catalina; Isidoro‐García, María; Dávila, Ignacio; Moreno, Esther; Laffond, Elena; Avila, Carmelo; Lorente, F.

doi:10.1111/j.1398-9995.2006.01025.x

Cited by 34 publications

(64 citation statements)

References 20 publications

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“…24 The genetic predisposition of the familial clusters may present as a single phenomenon, that is, post-coital preterm delivery, or in association with environmental factors as well. 26 PTGDR gene variability has been shown to be associated with a predilection to smooth bronchial muscle excitability in response to exogenous factors in specific ethnic groups, 29,30 and hence, the virtually uniform ethnicity across the groups in our study supports the (possible) genetic and environmental basis for this model. Abbreviation: CI, confidence interval; IPB, idiopathic preterm birth; PCPB, post-coital preterm birth.…”

Section: Discussionsupporting

confidence: 69%

Prostanoid DP receptor (PTGDR) variants in mothers with post-coital associated preterm births: preliminary observations

et al. 2009

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Objective: To describe prostanoid DP receptor (PTGDR) variants in women with preterm births who admitted to coital activity (CA) within 24 h of labor.Study Design: To achieve >80% statistical power, a pilot case-control study compared 24 premature births from mothers with CA (Group 1), 30 mothers of premature infants who did not have CA (Group 2 non-coital activity) and 95 non-coital activity mothers with term births (Group 3 controls). Four functional PTDGR single nucleotide polymorphisms (SNPs) were evaluated: T-549C, C-441/T, T-197C and G þ 1044A. PHASE 2.0.2 and SAS 9.2 were used for analysis.Result: All SNPs were in Hardy-Weinberg equilibrium in controls. The C-441/T genotype frequency was significantly increased among Group 1 women relative to Group 2 and 3 women (odds ratio (OR): 30.1, 95% confidence interval (CI) 6.9-191 and 25.7 95%CI 25.7-not computible, respectively). Of the possible haplotypes among the groups, the TCTG haplotype (T-549C, C-441/T, T-197C and G þ 1044A) was significantly more frequent in Group 1 women compared with the control groups (OR 53.4, ).Conclusions: A differential genomic pattern of PTGDR polymorphisms was identified in a sub-set of mothers which was associated with an increased risk of post-coital preterm birth.

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Section: Discussionsupporting

confidence: 69%

Prostanoid DP receptor (PTGDR) variants in mothers with post-coital associated preterm births: preliminary observations

et al. 2009

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“…The À441T/C polymorphism was associated with asthma development in the white population 11 but not in the Mexican population. 12 The À549T/C and À197T/C polymorphisms are associated with asthma development in the black 11 and Caucasian populations 13 , respectively. However, three SNPs were not significant in the Chinese population, as noted in our results.…”

Section: Discussionmentioning

confidence: 99%

“…The existence of genetic variants in the promoter region of the PTGDR (À549, À441 and À197) have been reported for several ethnic groups. [11][12][13][14] These three polymorphisms were not always related to asthma, but they may have a role in controlling PTGDR expression. Therefore, the PTGDR may serve as a therapeutic target for asthma.…”

Section: Introductionmentioning

confidence: 98%

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma

et al. 2011

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Activation of the prostaglandin D2 receptor (PTGDR) may contribute to pulmonary vasodilation, bronchoconstriction, recruitment of eosinophils, basophils and T-lymphocytes, and enhanced synthesis of leukotriene C4. We investigated whether polymorphisms of the leukotriene C4 synthase (LTC4S) À444A/C and PTGDR À441T/C were associated with clinical phenotypes and responsiveness to leukotriene receptor antagonist (LTRA) in Korean asthmatic children. We enrolled 270 normal and 870 asthmatic children. We prescribed montelukast (5 mg per day) to 100 of asthmatic children, and analyzed the responsiveness to LTRA by exercise challenge tests. Polymorphisms were genotyped by PCR-restriction fragment length polymorphism. As the number of minor alleles of the PTGDR À441T/C and LTC4S À444A/C polymorphisms increased, the log total eosinophil counts increased in atopic asthmatic children (P-value¼0.03). We found a significant association between responsiveness to montelukast and the PTGDR polymorphism (P-value¼0.038). However, the LTC4S À444A/C and PTGDR À441T/C were not associated with the susceptibility for asthma (LTC4S, AA versus AC+CC, adjusted odds ratio of 0.98 (95% confidence interval, 0.73-1.31); PTGDR, TT versus TC+CC, adjusted odds ratio of 0.90 (95% confidence interval, 0.68-1.19)) or clinical phenotypes (P-value40.05). The effects of the PTGDR and LTC4S polymorphisms on the enhancement of eosinophil counts were additive in the Korean children with asthma. In addition, the PTGDR polymorphism seems to be associated with the responsiveness to LTRA. Therefore, therapies that target the PTGDR may be useful for modulating the responsiveness to LTRA.

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“…Several studies indicated that the PTGDR variants in the promoter have functional impact on the expression of PTGDR. 10,11 The promoter SNP haplotypes (À549T/C, À441C/T, À197T/C) are shown to modify the PTGDR gene expression by altering the binding sites of the transcription factors, C/EBPb and members of the Sp and GATA families. 10 These transcription factors binding to the promoter are important for PTGDR transcription and the different SNPs change their binding efficiencies.…”

Section: Discussionmentioning

confidence: 99%

“…Oguma et al 10 reported replicated associations of a PTGDR variant with asthma from six markers genotyped by using a Caucasian American population with 518 cases and 175 controls (P ¼ 0.04) and an African American population with 80 cases and 45 controls (P ¼ 0.01). Sanz et al 11 showed the association of a PTGDR variant with asthma (P ¼ 0.007) from three markers genotyped in a Caucasian Spanish population with 118 cases and 79 controls. In contrast, Noguchi et al 12 failed to demonstrate the associations of PTGDR variants with asthma in an asthma population of 144 Japanese families with 476 subjects; Tsai et al 13 did not observe the significant associations with asthma in three populations analyzed: Puerto Ricans, Mexicans and African Americans.…”

Section: Introductionmentioning

confidence: 99%

Association of PTGDR gene polymorphisms with asthma in two Caucasian populations

et al. 2007

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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 (À731A/G) showed significant associations with asthma (P ¼ 0.0022), atopic asthma (P ¼ 0.0044), bronchial hyperreactivity or BHR (P ¼ 0.00120) and strict asthma (P ¼ 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 (o0.0031). An intronic polymorphism ( þ 6651C/T) also showed significant associations with asthma (P ¼ 0.0302), atopic asthma (P ¼ 0.0131), BHR (P ¼ 0.0249) and strict asthma (P ¼ 0.0261). In the Danish families, an intronic polymorphism ( þ 6541C/T) showed significant associations with asthma (P ¼ 0.0071), atopic asthma (P ¼ 0.0348), BHR (P ¼ 0.0033) and strict asthma (P ¼ 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.

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Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma

Cited by 34 publications

References 20 publications

Prostanoid DP receptor (PTGDR) variants in mothers with post-coital associated preterm births: preliminary observations

Prostanoid DP receptor (PTGDR) variants in mothers with post-coital associated preterm births: preliminary observations

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma

Association of PTGDR gene polymorphisms with asthma in two Caucasian populations

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