Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q99581 (FEV)
 3,296 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life.
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PMID:Respiratory damage in children exposed to urban pollution. 1283 95

IL10 is an anti-inflammatory cytokine that has been found to have lower production in macrophages and mononuclear cells from asthmatics. Since reduced IL10 levels may influence the severity of asthma phenotypes, we examined IL10 single-nucleotide polymorphisms (SNPs) for association with asthma severity and allergy phenotypes as quantitative traits. Utilizing DNA samples from 518 Caucasian asthmatic children from the Childhood Asthma Management Program (CAMP) and their parents, we genotyped six IL10 SNPs: 3 in the promoter, 2 in introns, and one in the 3' UTR. Using family-based association tests, each SNP was tested for association with asthma and allergy phenotypes individually. Population-based association analysis was performed with each SNP locus, the promoter haplotypes and the 6-loci haplotypes. The 3' UTR SNP was significantly associated with FEV(1) as a percent of predicted (FEV(1)PP) (P=0.0002) in both the family and population analyses. The promoter haplotype GCC was positively associated with IgE levels and FEV(1)PP (P=0.007 and 0.012, respectively). The promoter haplotype ATA was negatively associated with lnPC(20) and FEV(1)PP (P=0.008 and 0.043, respectively). Polymorphisms in IL10 are associated with asthma phenotypes in this cohort. Further studies of variation in the IL10 gene may help elucidate the mechanism of asthma development in children.
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PMID:IL10 gene polymorphisms are associated with asthma phenotypes in children. 1474 15

Severe alpha(1)-antitrypsin (AAT) deficiency is a proven genetic risk factor for chronic obstructive pulmonary disease (COPD), especially in individuals who smoke. There is marked variability in the development of lung disease in individuals homozygous (PI ZZ) for this autosomal recessive condition, suggesting that modifier genes could be important. We hypothesized that genetic determinants of obstructive lung disease may be modifiers of airflow obstruction in individuals with severe AAT deficiency. To identify modifier genes, we performed family-based association analyses for 10 genes previously associated with asthma and/or COPD, including IL10, TNF, GSTP1, NOS1, NOS3, SERPINA3, SERPINE2, SFTPB, TGFB1, and EPHX1. All analyses were performed in a cohort of 378 PI ZZ individuals from 167 families. Quantitative spirometric phenotypes included forced expiratory volume in one second (FEV(1)) and the ratio of FEV(1)/forced vital capacity (FVC). A qualitative phenotype of moderate-to-severe COPD was defined for individuals with FEV(1) </= 50 percent predicted. Six of 11 single-nucleotide polymorphisms (SNPs) in IL10 (P = 0.0005-0.05) and 3 of 5 SNPs in TNF (P = 0.01-0.05) were associated with FEV(1) and/or FEV(1)/FVC. IL10 SNPs also demonstrated association with the qualitative COPD phenotype. When phenotypes of individuals with a physician's diagnosis of asthma were excluded, IL10 SNPs remained significantly associated, suggesting that the association with airflow obstruction was independent of an association with asthma. Haplotype analysis of IL10 SNPs suggested the strongest association with IL10 promoter SNPs. IL10 is likely an important modifier gene for the development of COPD in individuals with severe AAT deficiency.
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PMID:IL10 polymorphisms are associated with airflow obstruction in severe alpha1-antitrypsin deficiency. 1769 Mar 29

The clinical course of cystic fibrosis (CF) varies considerably among patients carrying the same CF-causing gene mutation. Additional genetic modifiers may contribute to this variability. As airway inflammation is a key component of CF pathophysiology, we investigated whether major cytokine variants represent such modifiers in young CF patients. We tested 13 polymorphisms in 8 genes that play a key role in the inflammatory response: tumor necrosis factor, lymphotoxin alpha, interleukin (IL) 1B, IL1 receptor antagonist, IL6, IL8, IL10 and transforming growth factor beta 1 (TGFB1), for an association with lung disease progression and nutritional status in 329 CF patients. Variants in the TGFB1 gene at position +869T/C demonstrated a significant association with lung function decline. A less pronounced rate of decline in forced expiratory volume in 1 sec (FEV(1)) and forced vital capacity (FVC) were observed in patients heterozygous for TGFB1 +869 (+869CT), when compared to patients carrying either TGFB1 +869TT or +869CC genotypes. These findings support the concept that TGFB1 gene variants appear to be important genetic modifiers of lung disease progression in CF.
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PMID:Genetic variations in inflammatory mediators influence lung disease progression in cystic fibrosis. 1900 22