Disease relevance of MS4A2

• Atopy patch test skin was used as a model for acute inflammation in atopic dermatitis, while chronic lesional skin was used to investigate FcgammaR expression in chronically inflamed skin [1].
• The beta-subunit of the high-affinity IgE receptor (Fc epsilon RI-beta) on chromosome 11 is maternally linked to atopy, the state of enhanced IgE responsiveness underlying allergic asthma and rhinitis [2].
• An important locus for Atopy (familial asthma, hay fever and eczema) has been localized to the 11q12-q13 region with the minimum recombination fraction around the CD20 gene [3].
• Atopy and airways responsiveness in chronic obstructive pulmonary disease [4].
• Atopy is characterized by immediate immunoglobulin E (IgE)-mediated hypersensitivity to agents such as dust mites and pollen, and it underlies the increasingly prevalent disorder asthma [5].

Psychiatry related information on MS4A2

• Evidence linking psychological stress to the expression of asthma and atopy continues to grow [6].
• METHODS: In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086) [7].
• For example, we have characterised patients with type 1 brittle asthma, as defined in this review, on the basis of peak flow variability and treatment and these patients remain a separate group when assessed by other means such as psychosocial factors, immunoglobulin levels, and atopy [8].
• OBJECTIVE: The aim was to investigate the association between alcohol consumption and atopy (aeroallergen sensitization) [9].
• The risk reduction was stronger for allergies related to atopy (RR, 0.71; 95% CI, 0.64-0.80), but not for asthma (RR, 1.01; 95% CI, 0.77-1.31) [10].

High impact information on MS4A2

• Both of these approaches have implicated multiple regions in the human and mouse genomes, which are currently being evaluated as harboring putative atopy genes [11].
• Chromosome 13q14 shows consistent linkage to atopy and the total serum IgE concentration [12].
• We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420-->Lys variant shows significant association with atopy and AD in two independent panels of families [13].
• We obtained evidence for linkage in a 20-cM region of chromosome 7p14-p15 for three phenotypes: asthma, a high level of immunoglobulin E (IgE; atopy) and the combination of the phenotypes [14].
• The genetics of asthma and atopy have been difficult to determine because these diseases are genetically heterogeneous and modified by environment [14].

Chemical compound and disease context of MS4A2

• The patient had manifestations of atopy and an anaphylactic reaction following the administration of penicillin G [15].
• Is benzoic acid really harmful in cases of atopy and urticaria [16]?
• The monocyte-derived inflammatory mediator, prostaglandin E2 (PGE2), can reduce IFN-gamma production, and this in turn may relate to IL-4 up-regulation of IgE synthesis and impaired delayed hypersensitivity in atopy [17].
• METHODS: Pet exposure in the home was compared with cytokine secretion patterns (mitogen-stimulated mononuclear cells at birth and age 1 year) and indicators of atopy (allergen-specific and total IgE, eosinophilia, food allergy, atopic dermatitis) in 285 infants [18].
• CONCLUSIONS: These findings demonstrate that atopy, especially symptomatic latex allergy, is associated with AR during anesthesia in patients with spina bifida [19].

Biological context of MS4A2

• Our data indicate that Fc epsilon RI-beta, subject to maternal modification, may be the atopy-causing locus on chromosome 11q [2].
• We found that the beta subunit of the high-affinity receptor for IgE (Fc epsilon RI-beta) also lies on chromosome 11q13, and that it is in close genetic linkage with the gene for atopy [20].
• These results suggest that the SNPs in the FcepsilonRIbeta promoter are causally linked with atopy via regulation of FcepsilonRI expression [21].
• Polymorphisms in the Fc epsilon RI beta promoter region affecting transcription activity: a possible promoter-dependent mechanism for association between Fc epsilon RI beta and atopy [21].
• BACKGROUND: Atopic diseases are very common, and atopy has a strong genetic predisposition [22].

Anatomical context of MS4A2

• In atopy patch test sites no increase in the number of CD1a+ dendritic cells and a slight increase in macrophages compared with non-lesional skin was observed [1].
• The known roles of Fc epsilon RI in antigen-induced mast-cell degranulation and in the release of cytokines that enhance IgE production make the gene for its beta subunit a candidate for the chromosome 11 atopy locus [20].
• Two promising candidates for the atopy locus, the beta subunit of the high affinity immunoglobulin E receptor (Fc epsilon RI beta) and CD20, a molecule involved in B cell differentiation, have been placed within the contig [3].
• Twelve patients, 14 to 47 years of age, undergoing allogeneic bone marrow transplantation for the treatment of hematologic cancer were selected, along with their donors, by a screening questionnaire for a history of atopy in the donor [23].
• Asthma is a chronic inflammatory disease of the airways and lung mucosa with a strong correlation to atopy and acquired (IgE) immunity [24].

Associations of MS4A2 with chemical compounds

• Atopy is the genetic predisposition toward responses that result in the formation of large quantities of allergen-specific IgE [25].
• We examined the genetic linkage of the Fc epsilon RI beta gene with clinical asthma and the underlying phenotypes of BHR (to methacholine) and atopy (defined by skinprick testing) in 123 affected sibling-pairs recruited from the general population [26].
• Dietary vitamin E, IgE concentrations, and atopy [27].
• BACKGROUND: Distinct wheezing disorders co-exist in young (preschool) children, some of which (early transient wheeze and viral wheeze) are thought to be unrelated to atopy [28].
• These seven patients had higher serum total IgE antibody levels (328 [113-1,000] kU/I) than atopic patients without latex sensitization (n = 35; 124 [24-857] kU/I; P < 0.05) or patients without atopy (n = 70; 33 [2-339] kU/I; P < 0.001) [29].

Regulatory relationships of MS4A2

• CONCLUSION: Our findings indicate that the IL-4 receptor alpha gene does not exert a substantial influence on the inheritance of atopy or asthma in this Japanese population [30].
• OBJECTIVE: To assess whether the protective effect of farm exposure on atopy is influenced by a CD14 promoter functional polymorphism [31].
• We describe an association study designed to examine whether allelic variation at the glutathione-S-transferase GSTP1 locus influences expression of the BHR and atopy phenotypes in asthma [32].
• OBJECTICIVE: To examine whether FCER1B promoter polymorphisms (- 109C/T and - 654C/T) influence the genetic effects of the functional polymorphism (4G/5G) at the PAI-1 promoter region on asthma susceptibility using a case-control analysis [33].
• Furthermore, semi-quantitative RT-PCR analyses revealed marked down-modulation of a Th1 cytokine, interferon (IFN)-gamma, in IL-4-stimulated PBMC derived from atopy patients, but not that from healthy individuals [34].

Other interactions of MS4A2

• A 2.8 Mb YAC contig in 11q12-q13 localizes candidate genes for atopy: Fc epsilon RI beta and CD20 [3].
• Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor [2].
• By considering the probands and their spouses as an unrelated sample, we observed significant associations of atopy and asthma-related phenotypes with several IL4RA polymorphisms, including S478P and total serum IgE levels (P=.0007) [35].
• In whites in the CAMP cohort, the A allele of the IL12B G4237A polymorphism was undertransmitted to asthmatic children (P=.0008, recessive model), the global test for haplotypes for affection status was positive (P=.009, multiallelic chi (2)), and two polymorphisms were associated with different atopy phenotypes [36].
• Taken together, findings of the present study demonstrate that CCL18 is associated with an atopy/allergy skin phenotype, and is expressed at the interface between the environment and the host by cells constantly screening foreign Ags [37].

Analytical, diagnostic and therapeutic context of MS4A2

• Subjects with atopy were identified on the basis of an elevated serum IgE level (> or = 95 IU per milliliter) or a positive radioimmunosorbent test in response to standard inhalant allergens [22].
• Laboratory studies, food diaries, and skin tests were not helpful in establishing an etiology, although atopy was present in 12 of 15 patients tested [38].
• The risk of atopy in BCG-vaccinated children was not associated with age at vaccination (P =.17) [39].
• The positive association between measles and atopy was evident at all ages, in both urban and rural dwellers, and among subjects with many or few contacts at home or in day care [40].
• In a prenatally randomised, controlled study 120 infants with family history of atopy and high (greater than 0.5 kU/l) cord-blood concentrations of total IgE were allocated randomly to prophylactic and control groups [41].

References