Role of Prostanoid DP Receptor Variants in Susceptibility to Asthma

Oguma, Tsuyoshi; Palmer, Lyle J.; Birben, Esra; Sonna, Larry A.; Asano, Koichiro; Lilly, Craig M.

doi:10.1056/nejmoa031785

Cited by 129 publications

(185 citation statements)

References 31 publications

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“…Table 3 shows diplotype frequencies on the three loci, T-549C (locus 1), C-441T (locus 2) and T-197C (locus 3) in the human genome 14q22.1, which is given in Oguma et al (2004). Though the data is used for the genetic association studies in Oguma et al (2004), we simply consider fitting our models. As an example, we only consider the diplotype data of patients in the population of blacks (n = 79).…”

Section: The Analysis Of Ptgdr (Prostanoid Dp Receptor) Diplotype Frementioning

confidence: 99%

Markov basis and Gröbner basis of Segre–Veronese configuration for testing independence in group-wise selections

et al. 2008

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We consider testing independence in group-wise selections with some restrictions on combinations of choices. We present models for frequency data of selections for which it is easy to perform conditional tests by Markov chain Monte Carlo (MCMC) methods. When the restrictions on the combinations can be described in terms of a Segre-Veronese configuration, an explicit form of a Gröbner basis consisting of binomials of degree two is readily available for performing a Markov chain. We illustrate our setting with the National Center Test for university entrance examinations in Japan. We also apply our method to testing independence hypotheses involving genotypes at more than one locus or haplotypes of alleles on the same chromosome.

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Section: The Analysis Of Ptgdr (Prostanoid Dp Receptor) Diplotype Frementioning

confidence: 99%

Markov basis and Gröbner basis of Segre–Veronese configuration for testing independence in group-wise selections

et al. 2008

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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: 82%

“…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: 97%

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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“…15,16 The PTGDR are seven trans-membrane G-protein coupled receptors with an extracellular amino terminus and an intracellular carboxy terminus. 17,18 Sequence variants in PTGDR that posses a capacity for direct transcriptive regulation, T-549C, C-441T, T-197C and G þ 1044A, have been shown to be associated with the differential susceptibility of the bronchial smooth-muscle contraction response to excitatory stimuli 19 . Myometrial contraction is stimulated through these same receptors.…”

Section: Introductionmentioning

confidence: 99%

“…Myometrial contraction is stimulated through these same receptors. [19][20][21] Thus, a tenable hypothesis that we wished to test is whether functional variants of PTGDR may be involved in the possible but variable association between coitus and the onset of preterm labor…”

Section: Introductionmentioning

confidence: 99%

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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Role of Prostanoid DP Receptor Variants in Susceptibility to Asthma

Abstract: Our functional and genetic findings identify PTGDR as an asthma-susceptibility gene.

Cited by 129 publications

References 31 publications

Markov basis and Gröbner basis of Segre–Veronese configuration for testing independence in group-wise selections

Markov basis and Gröbner basis of Segre–Veronese configuration for testing independence in group-wise selections

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

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

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