Polymorphisms in IL12A and cockroach allergy in children with asthma

<p>Abstract</p> <p>Background</p> <p>IL12A has been implicated in T-cell development and may thus influence the development of atopy and allergic diseases.</p> <p>Methods</p> <p>We tested for association between four linkage disequilibrium (LD)-tagging SNPs (rs2243123, rs2243151, rs668998, and rs17826053) in <it>IL12A </it>and asthma and allergy-related (serum total and allergen-specific IgE, and skin test reactivity [STR] to two common allergens) phenotypes in two samples: 417 Costa Rican children with asthma and their parents, and 470 families of 503 white children in the Childhood Asthma Management Program (CAMP). The analysis was conducted using the family-based association test (FBAT) statistic implemented in the PBAT program.</p> <p>Results</p> <p>Among Costa Rican children with asthma, homozygosity for the minor allele of each of two SNPs in <it>IL12A </it>(rs2243123 and rs2243151) was associated with increased risks of STR to American cockroach (P ≤ 0.03 for both SNPs), STR to German cockroach (P ≤ 0.01 for both SNPs), and having a positive IgE to German cockroach (P < 0.05 for both SNPs). Among children in CAMP, homozygosity for the minor allele of SNP rs2243151 in <it>IL12A </it>was inversely associated with STR to German cockroach (P = 0.03) and homozygosity for the minor allele of SNP rs17826053 in <it>IL12A </it>was associated with increased risks of STR to American cockroach (P = 0.01) and STR to German cockroach (P = 0.007). There was no significant association between any SNP in <it>IL12A </it>and asthma, STR to dust mite, or total IgE in Costa Rica or CAMP.</p> <p>Conclusion</p> <p>Our findings suggest that variants in <it>IL12A </it>influence cockroach allergy among children with asthma.</p

IL1B polymorphisms modulate cystic fibrosis lung disease

Rationale: Variability in pulmonary disease severity is found in patients with cystic fibrosis (CF) who have identical mutations in the CF transmembrane conductance regulator (CFTR) gene. We hypothesized that one factor accounting for heterogeneity in pulmonary disease severity is variation in the family of genes affecting the biology of interleukin-1 (IL-1), which impacts acquisition and maintenance of Pseudomonas aeruginosa infection in animal models of chronic infection. Methods: We genotyped 58 single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster in 808 CF subjects from the University of North Carolina and Case Western Reserve University (UNC/CWRU) joint cohort. All were homozygous for ΔF508, and categories of “severe” (cases) or “mild” (control subjects) lung disease were defined by the lowest or highest quartile of forced expired volume (FEV1) for age in the CF population. After adjustment for age and gender, genotypic data were tested for association with lung disease severity. Odds ratios (ORs) comparing severe versus mild CF were also calculated for each genotype (with the homozygote major allele as the reference group) for all 58 SNPs. From these analyses, nine SNPs with a moderate effect size, OR ≤ 0.5or > 1.5, were selected for further testing. To replicate the case-control study results, we genotyped the same nine SNPs in a second population of CF parent-offspring trios (recruited from Children’s Hospital Boston), in which the offspring had similar pulmonary phenotypes. For the trio analysis, both family-based and population-based associations were performed. Results: SNPs rs1143634 and rs1143639 in the IL1B gene demonstrated a consistent association with lung disease severity categories (P < 0.10) and longitudinal analysis of lung disease severity (P < 0.10) in CF in both the case-control and family-based studies. In females, there was a consistent association (false discovery rate adjusted joint P-value < 0.06 for both SNPs) in both the analysis of lung disease severity in the UNC/CWRU cohort and the family-based analysis of affection status. Conclusion: Our findings suggest that IL1β is a clinically relevant modulator of CF lung disease

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Commissioning and performance of the CMS silicon strip tracker with cosmic ray muons

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPDuring autumn 2008, the Silicon Strip Tracker was operated with the full CMS experiment in a comprehensive test, in the presence of the 3.8 T magnetic field produced by the CMS superconducting solenoid. Cosmic ray muons were detected in the muon chambers and used to trigger the readout of all CMS sub-detectors. About 15 million events with a muon in the tracker were collected. The efficiency of hit and track reconstruction were measured to be higher than 99% and consistent with expectations from Monte Carlo simulation. This article details the commissioning and performance of the Silicon Strip Tracker with cosmic ray muons.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Precise mapping of the magnetic field in the CMS barrel yoke using cosmic rays

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPThe CMS detector is designed around a large 4 T superconducting solenoid, enclosed in a 12 000-tonne steel return yoke. A detailed map of the magnetic field is required for the accurate simulation and reconstruction of physics events in the CMS detector, not only in the inner tracking region inside the solenoid but also in the large and complex structure of the steel yoke, which is instrumented with muon chambers. Using a large sample of cosmic muon events collected by CMS in 2008, the field in the steel of the barrel yoke has been determined with a precision of 3 to 8% depending on the location.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Genome-Wide Association Study of Short-Acting β2-Agonists. A Novel Genome-Wide Significant Locus on Chromosome 2 near ASB3

Rationaleβ2-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable.ObjectivesTo investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma.MethodsWe performed a GWAS of acute bronchodilator response (BDR) to inhaled β2-agonists. A total of 444,088 single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the SNP Health Association Resource (SHARe) Asthma Resource Project (SHARP). The top 50 SNPs were carried forward to replication in a population of 444 individuals.Measurements and main resultsThe combined P value for four SNPs reached statistical genome-wide significance aftercorrecting for multiple comparisons. Combined P values for rs350729, rs1840321, rs1384918, and rs1319797 were 2.21 × 10(-10), 5.75 × 10(-8), 9.3 × 10(-8), and 3.95 × 10(-8), respectively. The significant variants all map to a novel genetic region on chromosome 2 near the ASB3 gene, a region associated with smooth muscle proliferation. As compared with the wild type, the presence of the minor alleles reduced the degree of BDR by 20% in the original population and by a similar percentage in the confirmatory population.ConclusionsThese GWAS findings for BDR in subjects with asthma suggest that a gene associated with smooth muscle proliferation may influence a proportion of the smooth muscle relaxation that occurs in asthma

Genome-Wide Association Study of Short-Acting beta(2)-Agonists A Novel Genome-Wide Significant Locus on Chromosome 2 near ASB3

Rationale: [beta(2)-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable. Objectives: To investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma. Methods: We performed a GWAS of acute bronchodilator response (BDR) to inhaled beta(2)-agonists. A total of 444,088 single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the SNP Health Association Resource (SHARe) Asthma Resource Project (SHARP). The top 50 SNPs were carried forward to replication in a population of 444 individuals. Measurements and Main Results: The combined P value for four SNPs reached statistical genome-wide significance after correcting for multiple comparisons. Combined P values for rs350729, rs1840321, rs1384918, and rs1319797 were 2:21 X 10(-10), 5.75 X 10(-8), 9.3 X 10(-8), 3.95 X 10(-8), respectively. The significant variants all map to a novel genetic region on chromosome 2 neat the ASB3 gene, a region associated with smooth muscle proliferation. As compared with the wild type, the presence of the minor alleles reduced the degree of BDR by 20% in the original population and by a similar percentage in the confirmatory population. Conclusions: These GWAS findings for BDR in subjects with asthma suggest that a gene associated with smooth muscle proliferation may influence a proportion of the smooth muscle relaxation that occurs in asthma