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Combined P (combined + p)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility gene

INFLAMMATORY BOWEL DISEASES, Issue 8 2007
J.R. Fraser Cummings MRCP(UK)
Abstract Background: A German genome-wide nonsynonymous single nucleotide polymorphism (nsSNP) association study identified ATG16L1 as a Crohn's disease (CD) susceptibility gene. The association appeared to be confined to the nsSNP rs2241880 and was confirmed in 2 German independent case-control collections (combined P = 4.0 × 10,8, odds ratio [OR] 1.45; 95% confidence interval [CI]: 1.21-1.74), a CD transmission disequilibrium test (TDT) collection, and an independent UK cohort. A weak statistical interaction with CARD15 was demonstrated. No association with ulcerative colitis (UC) was demonstrated. The aims of the study were to replicate the association with CD, examine subphenotype associations and statistical interactions with CARD15, IL23R, and the IBD5 risk haplotype, as well as explore the association with UC. Methods: The study included 645 CD and 676 UC rigorously phenotyped patients recruited from a single UK center. Unaffected controls comprised either spouses of patients (141) or individuals recruited from well-person clinics (1049). The nsSNP rs2241880 was genotyped using MassArray (Sequenom). Results: A strong association with CD was demonstrated (P = 2.33 × 10,7, OR 1.45 [1.25,1.67]), but no significant association was demonstrated with any subphenotype. We failed to replicate the reported interaction between rs2241880 and the CARD15 low-risk haplotypes dd and Dd. No significant statistical interaction with the 3 known CD susceptibility genes was seen. No association with UC susceptibility (P = 0.37, OR 1.06 [0.93-1.22]), or any UC subphenotype was identified. Conclusions: We confirmed the findings that ATG16L1 is a CD susceptibility gene and found no evidence of interaction with CARD15, IL23R, or IBD5. (Inflamm Bowel Dis 2007) [source]

Replication of the tumor necrosis factor receptor,associated factor 1/complement component 5 region as a susceptibility locus for rheumatoid arthritis in a European family-based study

ARTHRITIS & RHEUMATISM, Issue 9 2008
F. A. S. Kurreeman
Objective We recently showed, using a candidate gene approach in a case,control association study, that a 65-kb block encompassing tumor necrosis factor receptor,associated factor 1 (TRAF1) and C5 is strongly associated with rheumatoid arthritis (RA). Compared with case,control association studies, family-based studies have the added advantage of controlling potential differences in population structure and are not likely to be hampered by variation in population allele frequencies, as is seen for many genetic polymorphisms, including the TRAF1/C5 locus. The aim of this study was to confirm this association in populations of European origin by using a family-based approach. Methods A total of 1,356 western European white individuals from 452 "trio" families were genotyped for the rs10818488 polymorphism, using the TaqMan allelic discrimination assay. Results We observed evidence for association, demonstrating departure from Mendel's law, with an overtransmission of the rs10818488 A allele (A = 55%; P = 0.036). By taking into consideration parental phenotypes, we also observed an increased A allele frequency in affected versus unaffected parents (A = 64%; combined P = 0.015). Individuals carrying the A allele had a 1.2-fold increased risk of developing RA (allelic odds ratio 1.24, 95% confidence interval 1.04,1.50). Conclusion Using a family-based study that is robust against population stratification, we provide evidence for the association of the TRAF1/C5 rs10818488 A allele and RA in populations of European descent, further substantiating our previous findings. Future functional studies should yield insight into the biologic relevance of this locus to the pathways involved in RA. [source]

SNCA variants are associated with increased risk for multiple system atrophy,,

ANNALS OF NEUROLOGY, Issue 5 2009
Sonja W. Scholz MD
To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome-wide association study of Parkinson's disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.5 × 1012; odds ratio 6.2). Ann Neurol 2009;65:610,614 [source]

Investigating the potential of Bacillus subtilis ,-amylase as a pressure-temperature-time indicator for high hydrostatic pressure pasteurization processes

BIOTECHNOLOGY PROGRESS, Issue 4 2009
Tara Grauwet
Abstract The potential of Bacillus subtilis ,-amylase (BSA) as a pressure-temperature-time indicator (pTTI) for high pressure pasteurization processing (400,600 MPa; Ti 10,40°C; 1,15 min) was investigated. A stepwise approach was followed for the development of an enzyme-based, extrinsic, isolated pTTI. First, based on literature data on the pressure stability, BSA was selected as a candidate indicator. Next to the accuracy and ease of the measurement of the indicator's response (residual activity) to the pressure treatment, the storage and handling stability of BSA at atmospheric pressure was verified. Second, the stability of BSA at a constant temperature (T) and time in function of pressure (p) was investigated. Solvent engineering was used to shift the inactivation window of BSA in the processing range of interest. Third, the enzyme (1 g/L BSA,MES 0.05 M pH 5.0) was kinetically calibrated under isobaric-isothermal conditions. Time dependent changes in activity could be modeled best by a first-order model. Except for low pressures and high temperatures, a synergistic effect between pressure and temperature could be observed. Based on the model selected to describe the combined p,T-dependency of the inactivation rate constant, an elliptically shaped isorate contour plot could be constructed, illustrating the processing range where BSA can be used to demonstrate temperature gradients. Fourth, the validity of the kinetic model was tested successfully under dynamic conditions similar to those used in food industry. Finally, the indicator was found suitable to demonstrate nonuniformity in two-sectional planes of a vertical, single vessel system. © 2009 American Institute of Chemical Engineers. Biotechnol. Prog., 2009 [source]