RESUMO
Sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) promotes the apoptosis of eosinophils and inhibits FcvarepsilonRI-dependent mediator release from mast cells. We investigated the genetic association between sequence variants in Siglec-8 and diagnosis of asthma, total levels of serum IgE (tIgE), and diagnosis of eosinophilic esophagitis (EE) in diverse populations. The effect of sequence variants on Siglec-8 glycan ligand-binding activity was also examined. Significant association with asthma was observed for SNP rs36498 (odds ratios (OR), 0.69, P=8.8 x 10(-5)) among African Americans and for SNP rs10409962 (Ser/Pro) in the Japanese population (OR, 0.69, P=0.019). Supporting this finding, we observed association between SNP rs36498 and current asthma among Brazilian families (P=0.013). Significant association with tIgE was observed for SNP rs6509541 among African Americans (P=0.016), and replicated among the Brazilian families (P=0.02). In contrast, no association was observed with EE in Caucasians. By using a synthetic polymer decorated with 6'-sulfo-sLe(x), a known Siglec-8 glycan ligand, we did not find any differences between the ligand-binding activity of HEK293 cells stably transfected with the rs10409962 risk allele or the WT allele. However, our association results suggest that the Siglec8 gene may be a susceptibility locus for asthma.
Assuntos
Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos B/genética , Asma/genética , Predisposição Genética para Doença , Lectinas/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Negro ou Afro-Americano/genética , Povo Asiático/genética , Asma/etnologia , Brasil , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/fisiologia , População Branca/genética , Adulto JovemRESUMO
Evolving relationships between electrical conductivity (EC) and sodium adsorption ratio (SAR) in reconstructed soils at surface mines have been insufficiently documented in the literature. Some minesoils (i.e., rootzone material) are classified as saline, sodic, or saline-sodic and are considered unsuitable for revegetation. Weatherable minerals such as calcite and gypsum are common in alkaline minesoils and on dissolution tend to mitigate elevated SAR levels by maintaining or increasing electrolytes in the soil and providing sources of exchangeable calcium and magnesium. Topsoils (i.e., coversoils) contribute to mitigation of sodic conditions when soluble cations are translocated from coversoils into the underlying minesoils. This study evaluated the weathering characteristics of minesoils sites from three surface coal mines in northwestern New Mexico and northeastern Arizona. Minesoils were grouped into 11 classes based on EC and SAR. After 6 to 14 yr, differences between upper and lower halves of the coversoils suggest general increases occurred with EC, SAR, chloride (Cl(-)), and sulfate (SO(4)(2-)) with depth. Within the reclaimed minesoils, there were several significant (P < 0.05 or < 0.10) relationships among EC and SAR that related to Minesoil Class. Lower SAR levels with corresponding increases in EC compared to baseline minesoils were more apparent in upper minesoil depths (0-5 and 5-15 cm). Minesoil anion concentrations suggested coversoil leachates and gypsum dissolution influenced EC and SAR chemistry. Over time, chemical changes have increased the apparent stability of the saline and sodic reclaimed minesoils studied thereby reducing risks associated with potential aggregate slaking and clay particle dispersion.
Assuntos
Salinidade , Sódio/análise , Solo/análise , Arizona , Cátions/análise , Condutividade Elétrica , Recuperação e Remediação Ambiental , Resíduos Industriais , Mineração , New Mexico , Tempo (Meteorologia)RESUMO
BACKGROUND: Asthma is a complex disease characterized by a high prevalence of allergic diathesis and the almost ubiquitous presence of upper airway disease (eg rhinitis). Previously, we observed linkage of asthma among Afro-Caribbean families to markers in chromosome 12q, which contains a number of genes encoding for products closely related to allergic airway inflammation and disease. OBJECTIVE: To identify susceptibility loci in chromosome 12q contributing to the genetics of upper and lower airway diseases and to expand the region to include genes encoding IFN- ã(IFNG) and one of the signal transducers and activators of transcription (STAT6), we conducted further linkage studies among 33 multiplex families. METHODS: We characterized 528 subjects from Barbados for asthma; 82 percent were characterized for allergic rhinitis. Two-point and multipoint linkage analysis of 22 microsatellite markers (spanning ~79 centimorgan) was performed. RESULTS: Affected sib-pair analysis revealed significant evidence for linkage to asthma over approximately 30 cM (P < .05 to .002), with the best evidence for linkage at a CA repeat polymorphism in the first intron of IFNG in 12q21.1 (P = .002). Evidence of linkage to allergic rhinitis was observed in the same region (D12S313, P = .006, and IFNGCA, P = .01. respectively). Multipoint linkage analysis also provided evidence for linkage to asthma, with the best nonparametric linkage analysis score at D12S326 (nonparametric linkage score = 3.8, P = .0008). Modest evidence for linkage to allergic rhinitis was observed next to D12S326 at D12S1052 (p = .036) CONCLUSIONS: Our findings suggest that (1) one or more loci in the chromosome 12q13.12-q23.3 region are contributing to the expresstion of the clinical phenotype asthma and the strongest evidence for linkage is in a region near the gene encoding IFNG and (2) a susceptibility locus for both asthma and allergic rhinitis maps to this region.