Allergy to &lt;i&gt;Dermatophagoides&lt;/i&gt; in a Group of Spanish Gypsies: Genetic Restrictions

Cárdaba, Blanca; Moffatt, Miriam F.; Fernández, E.; Jurado, Aurora; Rojo, Marta; García, Milagros; Ansotegui, Ignacio J.; Cortegano, Isabel; Arrieta, Ignacio; Etxenagusia, M.; Pozo, Victoria del; Urraca, Javier; Aceituno, Esther; Gallardo, Soledad; Palomino, Pilar; Cookson, William; Lahoz, Carlos

doi:10.1159/000053830

Cited by 17 publications

(10 citation statements)

References 34 publications

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“…The GWAS result is in line with previous observations from genome-wide linkage searches that identified linkage between 6p/6p21/6p21.3 locus and total and/or specific serum IgE levels [234,240,241]. Candidate gene studies also reported associations between HLA-DRB1/HLA-DRB1 alleles/markers and total and/or specific serum IgE levels [242][243][244][245][246].…”

Section: Chromosome 6p213 Hla-drb1supporting

confidence: 90%

Current concepts of IgE regulation and impact of genetic determinants

Potaczek

Kabesch

2012

Clin Experimental Allergy

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Immunoglobulin E (IgE) mediated immune responses seem to be directed against parasites and neoplasms, but are best known for their involvement in allergies. The IgE network is tightly controlled at different levels as outlined in this review. Genetic determinants were suspected to influence IgE regulation and IgE levels considerably for many years. Linkage and candidate gene studies suggested a number of loci and genes to correlate with total serum IgE levels, and recently genome-wide association studies (GWAS) provided the power to identify genetic determinants for total serum IgE levels: 1q23 (FCER1A), 5q31 (RAD50, IL13, IL4), 12q13 (STAT6), 6p21.3 (HLA-DRB1) and 16p12 (IL4R, IL21R). In this review, we analyse the potential role of these GWAS hits in the IgE network and suggest mechanisms of how genes and genetic variants in these loci may influence IgE regulation.

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Section: Chromosome 6p213 Hla-drb1supporting

confidence: 90%

Current concepts of IgE regulation and impact of genetic determinants

Potaczek

Kabesch

2012

Clin Experimental Allergy

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“…Eight studies were excluded for the following reasons: sibling paired and family based study design (n = 2), 8 25 no allele or genotyping frequency (n = 3), 7 14 20 and analysis of the TNFb (lymphotoxin-a, LTa) NcoI polymorphism rather than TNFa (n = 5). [33][34][35][36][37] Fifteen original case-control studies, comprising 2409 patients with asthma and 3266 controls, were included in the meta-analysis (table 1). 6 9-13 15-19 21-24 Seven were performed in Caucasian subjects, 6 9 11-13 16 24 two in Italian subjects, 18 19 four in East Asian populations, 17 21-23 one in a South Asian population, 12 and two in a mixed race cohort.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Association between polymorphism of tumour necrosis factor -308 gene promoter and asthma: a meta-analysis

Gao

Shan

Sun

et al. 2006

Thorax

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Background: Asthma is a complex polygenic disease in which gene-environment interactions are important. The gene encoding tumour necrosis factor alpha (TNFa) is one of several candidate loci for asthma pathogenesis and is highly polymorphic. A number of studies have investigated the polymorphism of TNFa-308 gene promoter (substitution GRA, designated as TNF1 and TNF2) in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent. Methods: To address the inconsistent findings in studies of the association of the polymorphism of TNFa-308 gene promoter with susceptibility to asthma, a systematic review was undertaken of the published data and a meta-analysis was performed. The MEDLINE database was searched for case-control studies published in English language journals from 1966 to October 2005. Data were extracted using standardised forms and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Fifteen eligible studies, comprising 2409 patients with asthma and 3266 controls, were included in the meta-analysis. Using the random effects model, the pooled result showed that the TNF2 allele is associated with overall susceptibility to asthma (OR 1.37, 95% CI 1.02 to 1.84, p = 0.04). The ORs for asthma susceptibility in TNF2 homozygote individuals were significantly increased at 2.01 (95% CI 1.26 to 3.20, p = 0.009) and 1.51 (95% CI 1.02 to 2.22, p = 0.041) compared with TNF1 homozygotes and TNF2/1 heterozygotes, respectively. In addition, the pooled OR for asthma risk in TNF2/1 heterozygotes was also significantly higher than that in TNF1/1 homozygotes (OR 1.47, 95% CI 1.01 to 2.13, p = 0.045). Conclusions: The TNF2 allele confers a significant risk for developing asthma. A large scale case-control study is needed to clarify the functional effect of the polymorphism of the TNFa gene in the pathogenesis of asthma.

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“…As shown in Figure 1, the LTA gene, previously called the TNF-␤ gene, is located close upstream to the TNF gene. An NcoI polymorphism in the LTA gene has also been associated with asthma in children (19) and adults (5), although each study reported that a different allele was associated and 13 other studies (4,7,9,11,13,14,16,17,20,(23)(24)(25)(26) showed no association (see Table 1). …”

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confidence: 98%

Extended Haplotype in the Tumor Necrosis Factor Gene Cluster Is Associated with Asthma and Asthma-related Phenotypes

Randolph

Lange

Silverman

et al. 2005

Am J Respir Crit Care Med

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Rationale: Tumor necrosis factor is a proinflammatory cytokine found in increased concentrations in asthmatic airways. The TNF-␣ (TNF) and lymphotoxin-␣ (LTA) genes belong to the TNF gene superfamily located within the human major histocompatibility complex on chromosome 6p in a region repeatedly linked to asthma. The TNF position -308 and LTA NcoI polymorphisms are believed to influence TNF transcription and secretion, respectively. Objectives: This study sought to determine whether polymorphisms in TNF or LTA, or in TNF-LTA haplotypes, are associated with asthma and asthma phenotypes. Methods: We genotyped the TNF -308 and LTA NcoI polymorphisms, and two other haplotype-tagging polymorphisms in the TNF and LTA genes, in 708 children with mild to moderate asthma enrolled in the Childhood Asthma Management Program and in their parents. Using an extension of the family-based association tests in the PBAT program, each polymorphism was tested for association with asthma, age at onset of asthma, and time series data on baseline FEV 1 % predicted, postbronchodilator FEV 1 % predicted, body mass index, and log of PC 20 . Measurements and Main Results: Although no associations were found for the individual single-nucleotide polymorphisms, the haplotype analysis found the LTA NcoI_G/LTA 4371T/TNF -308G/TNF 1078G haplotype to be associated with asthma and with all five phenotype groups. Conclusions: We conclude that it is unlikely that the TNF -308 or LTA NcoI polymorphisms influence asthma susceptibility individually, but that this haplotype of variants may be functional or may be in linkage disequilibrium with other functional single-nucleotide polymorphisms.

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Allergy to <i>Dermatophagoides</i> in a Group of Spanish Gypsies: Genetic Restrictions

Cited by 17 publications

References 34 publications

Current concepts of IgE regulation and impact of genetic determinants

Current concepts of IgE regulation and impact of genetic determinants

Association between polymorphism of tumour necrosis factor -308 gene promoter and asthma: a meta-analysis

Extended Haplotype in the Tumor Necrosis Factor Gene Cluster Is Associated with Asthma and Asthma-related Phenotypes

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