Haplotypes of G Protein–coupled Receptor 154 Are Associated with Childhood Allergy and Asthma

Melén, Erik; Bruce, Sara; Doekes, Gert; Kabesch, Michael; Laitinen, Tarja; Lauener, Roger; Lindgren, Cecilia M.; Riedler, Josef; Scheynius, Annika; Hage‐Hamsten, M. van; Kere, Juha; Pershagen, Göran; Wickman, Magnus; Nyberg, Fredrik

doi:10.1164/rccm.200410-1317oc

Cited by 105 publications

(90 citation statements)

References 28 publications

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“…However, six other studies did not detect associations of rs323922 with either asthma or atopy in Koreans, Chinese, Germans, Italians and a mixed population from five Western European countries. [2][3][4][5][6][7] We did not observe an association between rs323922 and asthma or atopy in Mexican population either. For other GPRA SNPs, findings also vary across populations (Table 5).…”

Section: Discussioncontrasting

confidence: 73%

“…5 The H4 haplotype was also associated with asthma in a German population. 2 The H5 haplotype was associated with high IgE in the Finnish population, 1 with asthma risk in a mixed population from five Western European countries 3 and with protective effect of asthma in the Italian population. 5 The H4 and H5 haplotypes are rare in Mexican population (frequency o5%).…”

Section: Discussionmentioning

confidence: 98%

“…For other GPRA SNPs, findings also vary across populations (Table 5). For example, associations with asthma phenotypes have been found for SNP546333 and rs740347 in the German 2 and Italian 5 populations, for rs324396 in Germans 2 and the mixed population from five Western European countries, 3 for rs324384 in the mixed population from five Western European countries 3 and for rs324981 in the Chinese population 4 (Table 5). The 27 SNPs analyzed in our study, including the above SNPs or SNPs in high LD with above SNPs, were representative of the GPRA gene.…”

Section: Discussionmentioning

confidence: 99%

“…1 However, this finding was not confirmed in other populations. [2][3][4][5][6][7] The H4 haplotype conferred the risk for high serum IgE in a Finnish population, 1 but played a protective role in an Italian population. 5 The H4 haplotype was also associated with asthma in a German population.…”

Section: Discussionmentioning

confidence: 99%

“…GPRA single nucleotide polymorphisms (SNPs) and haplotypes have been associated with asthma or atopy in several studies, [1][2][3][4][5] but not in others. 6,7 In the studies in which associations have been found, however, the SNPs and haplotypes related to asthma and atopy are inconsistent across populations.…”

Section: Introductionmentioning

confidence: 99%

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Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy

Romieu

Sienra-Monge

et al. 2008

Genes Immun

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G-protein-coupled receptor for asthma susceptibility (GPRA or GPR154) was identified as an asthma and atopy candidate gene by positional cloning. Some subsequent studies suggest associations of GPRA single nucleotide polymorphisms (SNPs) and haplotypes with asthma or atopy susceptibility. However, the associated SNPs or haplotypes vary among studies. The role of GPRA genetic variation in asthma and atopy remains unsolved. Published data on GRPA variants and asthma come exclusively from Caucasian and Asian populations. We examined whether GPRA SNPs and haplotypes are associated with asthma and atopy in a Mexican population. We genotyped and analyzed 27 GPRA SNPs in 589 nuclear families consisting of asthmatic children aged 4-17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests to 25 aeroallergens. The 27 SNPs examined provided excellent coverage of the GPRA gene. GPRA SNPs and haplotypes were not associated with childhood asthma and the degree of atopy to aeroallergens in a Mexican population. Our review of studies of GPRA variants in relation to asthma phenotypes shows considerable heterogeneity. Accordingly, our results suggest that GPRA variants are not an important contributor to childhood asthma and atopy susceptibility in a Mexican population.

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Section: Discussioncontrasting

confidence: 73%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy

Romieu

Sienra-Monge

et al. 2008

Genes Immun

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Molecular Modeling Studies on the Human Neuropeptide S Receptor and Its Antagonists

et al. 2010

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Neuropeptide S (NPS) is a 20-residue peptide of great interest due to its potential involvement in several biological processes such as arousal, anxiety, and food intake. The NPS receptor belongs to the rhodopsin-like G-protein-coupled receptor superfamily, and several polymorphisms and isoforms of this receptor are associated with asthma, allergies, and bronchial hyper-responsiveness, in particular the Asn 107 Ile mutation. Limited structural information is available for this peptide-receptor system, particularly regarding the NPS receptor structure, its nonpeptide ligands, and the molecular aspects of agonist and antagonist binding processes. In this work, rhodopsin-based homology models of the NPS receptor and its Asn 107 Ile variant were built and refined in a membrane bilayer model, and binding modes for nonpeptide antagonists were simulated. This study provides the first structural study of the human NPS receptor, and the results provide a starting point for further characterization of the binding modes of its antagonists, and for the rational design of new NPS receptor ligands.

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Neuropeptide S Receptor: Recent Updates on Nonpeptide Antagonist Discovery

et al. 2011

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Neuropeptide S (NPS) is a 20-amino acid peptide of great interest due to its possible involvement in several biological processes, including food intake, locomotion, wakefulness, arousal, and anxiety. Structure-activity relationship studies of NPS have identified key points for structural modifications with the goal of modulating NPS receptor (NPSR) agonist activity or achieving antagonism at the same receptor. Only limited information is available for nonpeptide NPSR antagonists. In the last year, several studies have been reported in literature which present various series of small molecules as antagonists of this receptor. The results allow a comparison of the structures and activities of these molecules, leading to the design of new ligands with increased potency and improved pharmacological and pharmacokinetic profiles. This work presents a brief overview of the available information regarding structural features and pharmacological characterization of published nonpeptide NPSR antagonists.

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Haplotypes of G Protein–coupled Receptor 154 Are Associated with Childhood Allergy and Asthma

Abstract: Our results indicate that polymorphisms and haplotypes in the haplotype block of GPR154 are associated with asthma, rhinoconjunctivitis, and sensitization in European children.

Cited by 105 publications

References 28 publications

Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy

Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy

Molecular Modeling Studies on the Human Neuropeptide S Receptor and Its Antagonists

Neuropeptide S Receptor: Recent Updates on Nonpeptide Antagonist Discovery

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