SNPs in the FCER1A Gene Region Show No Association with Allergic Rhinitis in a Han Chinese Population

Background: Immunoglobulin E (IgE) is a central player in the allergic response, and raised total IgE levels are considered as an indicator of atopy or potential development of atopy. A recent genome-wide scan in a German population-based cohort of adults identified the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) as a susceptibility locus influencing total serum IgE levels. The aim of this study was to investigate whether the polymorphisms in the FCER1A gene are associated with allergic rhinitis (AR) in a Han Chinese population. Methodology/Principal Findings: A population of 378 patients with AR and 288 healthy controls was studied. Precise phenotyping of patients was accomplished by means of a questionnaire and clinical examination. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE) measurement. A total of 16 single nucleotide polymorphisms (SNPs) in FCER1A were selected and individually genotyped. None of the SNPs in the FCER1A showed an association with AR. Similarly, the lack of association was also evident in subgroup analysis for the presence of different allergen sensitivities. None of the selected SNPs in FCER1A was associated with total IgE level. Conclusions: Although FCER1A presents itself as a good candidate for contributing to total serum IgE, this study failed t

Epistasis between FLG and IL4R genes on the risk of allergic sensitization: results from two population-based birth cohort studies

Immune-specifc genes as well as genes responsible for the formation and integrity of the epidermal barrier have been implicated in the pathogeneses of allergic sensitization. This study sought to determine whether an epistatic efect (gene-gene interaction) between genetic variants within interleukin 4 receptor (IL4R) and flaggrin (FLG) genes predispose to the development of allergic sensitization. Data from two birth cohort studies were analyzed, namely the Isle of Wight (IOW; n=1,456) and the Manchester Asthma and Allergy Study (MAAS; n=1,058). In the IOW study, one interaction term (IL4R rs3024676×FLG variants) showed statistical signifcance (interaction term: P=0.003). To illustrate the observed epistasis, stratifed analyses were performed, which showed that FLG variants were associated with allergic sensitization only among IL4R rs3024676 homozygotes (OR, 1.97; 95% CI, 1.27–3.05; P=0.003). In contrast, FLG variants efect was masked among IL4R rs3024676 heterozygotes (OR, 0.53; 95% CI, 0.22–1.32; P=0.175). Similar results were demonstrated in the MAAS study. Epistasis between immune (IL4R) and skin (FLG) regulatory genes exist in the pathogenesis of allergic sensitization. Hence, genetic susceptibility towards defective epidermal barrier and deviated immune responses could work together in the development of allergic sensitization

Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population

<p>Abstract</p> <p>Background</p> <p>Asthma and allergy represent complex phenotypes, which disproportionately burden ethnic minorities in the United States. Strong evidence for genomic factors predisposing subjects to asthma/allergy is available. However, methods to utilize this information to identify high risk groups are variable and replication of genetic associations in African Americans is warranted.</p> <p>Methods</p> <p>We evaluated 41 single nucleotide polymorphisms (SNP) and a deletion corresponding to 11 genes demonstrating association with asthma in the literature, for association with asthma, atopy, testing positive for food allergens, eosinophilia, and total serum IgE among 141 African American children living in Detroit, Michigan. Independent SNP and haplotype associations were investigated for association with each trait, and subsequently assessed in concert using a genetic risk score (GRS).</p> <p>Results</p> <p>Statistically significant associations with asthma were observed for SNPs in <it>GSTM1, MS4A2</it>, and <it>GSTP1 </it>genes, after correction for multiple testing. Chromosome 11 haplotype CTACGAGGCC (corresponding to <it>MS4A2 </it>rs574700, rs1441586, rs556917, rs502581, rs502419 and <it>GSTP1 </it>rs6591256, rs17593068, rs1695, rs1871042, rs947895) was associated with a nearly five-fold increase in the odds of asthma (Odds Ratio (OR) = 4.8, <it>p </it>= 0.007). The GRS was significantly associated with a higher odds of asthma (OR = 1.61, 95% Confidence Interval = 1.21, 2.13; <it>p </it>= 0.001).</p> <p>Conclusions</p> <p>Variation in genes associated with asthma in predominantly non-African ethnic groups contributed to increased odds of asthma in this African American study population. Evaluating all significant variants in concert helped to identify the highest risk subset of this group.</p

Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

Background: Schistosomiasis is still a major public health burden in the tropics and subtropics. Although there is an effective chemotherapy (Praziquantel) for this disease, reinfection occurs rapidly after mass drug administration (MDA). Because the entire population do not get reinfected at the same rate, it is possible that host factors may play a dominant role in determining resistance or susceptibility to reinfection with schistosomes. Here, we systematically reviewed and meta-analyzed studies that reported associations between reinfection with the principal human-infecting species (S. mansoni, S. japonicum and S. haematobium) and host socio-demographic, epidemiological, immunological and genetic factors.Methodology/Principal Findings: PubMed, Scopus, Google Scholar, Cochrane Review Library and African Journals Online public databases were searched in October 2013 to retrieve studies assessing association of host factors with reinfection with schistosomes. Meta-analysis was performed to generate pooled odds ratios and standardized mean differences as overall effect estimates for dichotomous and continuous variables, respectively. Quality assessment of included studies, heterogeneity between studies and publication bias were also assessed. Out of the initial 2739 records, 109 studies were included in the analyses, of which only 32 studies with 37 data sets were eligible for quantitative data synthesis. Among several host factors identified, strong positive association was found with age and pre-treatment intensity, and only slightly for gender. These factors are major determinants of exposure and disease transmission. Significant positive association was found with anti-SWA IgG4 level, and a negative overall effect for association with IgE levels. This reconfirmed the concept that IgE/IgG4 balance is a major determinant of protective immunity against schistosomiasis. Other identified determinants were reported by a small number of studies to enable interpretation.Conclusions: Our data contribute to the understanding of host-parasite interaction as it affects reinfection, and is a potential tool to guide planning and tailoring of community interventions to target high-risk groups