4 results on '"Newman, William G."'
Search Results
2. Genetic variants in IL-23R and ATG16L1 independently predispose to increased susceptibility to Crohn's disease in a Canadian population.
- Author
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Newman WG, Zhang Q, Liu X, Amos CI, and Siminovitch KA
- Subjects
- Autophagy-Related Proteins, Canada, Case-Control Studies, Colitis, Ulcerative ethnology, Crohn Disease ethnology, Gene Frequency, Genetic Predisposition to Disease, Humans, Jews genetics, Logistic Models, Odds Ratio, Risk Assessment, Risk Factors, White People genetics, Carrier Proteins genetics, Colitis, Ulcerative genetics, Crohn Disease genetics, Polymorphism, Single Nucleotide, Receptors, Interleukin genetics
- Abstract
Goals: To establish the relevance of variants in the IL-23R and ATG16L1 genes in inflammatory bowel disease (IBD)., Aim: Three recent genome wide association studies have identified variants in the IL-23R and ATG16L1 genes, which modulate susceptibility to Crohn's disease (CD)., Methods: We genotyped 1028 IBD patients, including 443 CD and 347 ulcerative colitis (UC) non-Jewish cases, 238 (183 CD and 55 UC) Jewish cases, and 1005 ethnically matched control subjects for 18 and 11 variants, respectively, in the IL-23R and ATG16L1 genes, including the IL-23R (R381Q) and ATG16L1 (T216A) variants, previously associated with CD., Results: Single nucleotide polymorphisms within each of 3 haplotype blocks across the IL-23R gene were associated with an increased risk of CD. Notably, the minor allele of the IL-23R R381Q variant was present in 2.9% of cases and 6.0% controls (P=0.0001, odds ratio=0.48, 95% confidence interval 0.33-0.69). Homozygosity for the minor (T) allele of the ATG16L1 T216A polymorphism was strongly protective for CD (P=0.0001, odds ratio=0.51, 95% confidence interval 0.38-0.68). No phenotypic associations were detected and no interactions between the genes to increase disease risk were established., Conclusions: We confirm the association of CD with variants in the IL-23R and ATG16L1 genes and the more modest association of the IL-23R R381Q variant with UC. Our results also suggest that these variants act independently of one another to influence risk and pathogenesis of IBD.
- Published
- 2009
- Full Text
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3. Rheumatoid arthritis association with the FCRL3 -169C polymorphism is restricted to PTPN22 1858T-homozygous individuals in a Canadian population.
- Author
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Newman WG, Zhang Q, Liu X, Walker E, Ternan H, Owen J, Johnson B, Greer W, Mosher DP, Maksymowych WP, Bykerk VP, Keystone EC, Amos CI, and Siminovitch KA
- Subjects
- Adult, Canada, Epistasis, Genetic, Female, Homozygote, Humans, Male, Middle Aged, Odds Ratio, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Risk Factors, Thyroiditis, Autoimmune diagnosis, Thyroiditis, Autoimmune genetics, Thyroiditis, Autoimmune immunology, Arthritis, Rheumatoid genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics, Protein Tyrosine Phosphatases genetics, Receptors, Immunologic genetics
- Abstract
Objective: Variants in genes encoding the Fc receptor-like 3 (FcRL-3) and the class II major histocompatibility complex (MHC) transactivator proteins have been associated with an increased risk of rheumatoid arthritis (RA) in Japanese and Nordic populations, respectively. The aim of this study was to investigate these associations in a Canadian Caucasian cohort of RA cases and healthy controls., Methods: A total of 1,187 RA patients and 462 healthy controls were genotyped for FCRL3 and MHC2TA gene variants associated with RA. Epistasis between the FCRL3 -169C and the PTPN22 1858T variants was also examined., Results: An association was detected between RA and both the FCRL3 -169C allele (OR 1.19, P = 0.023) and the homozygous genotype (OR 1.41, P = 0.027), but association of the MHC2TA promoter region variant (-168G) with RA was not replicated. Stratification of the RA cohort by PTPN22 genotypes revealed the FCRL3 risk variant and RA association was stronger in the patient subgroup lacking PTPN22 1858T variants (P = 0.004) and was not detectable in the subgroup with PTPN22 1858T variants (P = 0.52). The PTPN22 association with RA was greater in the absence than in the presence of the FCRL3 -169C allele (P = 0.0008 versus P = 0.001). The PTPN22 1858T variant also increased the risk of autoimmune thyroid disease (AITD) in the RA patients, whereas the FCRL3 risk variant was protective against AITD., Conclusion: Our findings support an association of RA with an FCRL3 functional polymorphism and reveal that this association is stronger in the absence of PTPN22 risk genotypes. These findings support a genetic heterogeneity across RA populations, suggesting that both the FCRL3 and PTPN22 genes play roles in RA susceptibility, but in different individuals.
- Published
- 2006
- Full Text
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4. DLG5 variants contribute to Crohn disease risk in a Canadian population.
- Author
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Newman WG, Gu X, Wintle RF, Liu X, van Oene M, Amos CI, and Siminovitch KA
- Subjects
- Adult, Canada, Case-Control Studies, Colitis, Ulcerative genetics, Gene Frequency, Genotype, Humans, Polymorphism, Single Nucleotide genetics, Risk Factors, Crohn Disease ethnology, Crohn Disease genetics, Genetic Predisposition to Disease, Membrane Proteins genetics, Tumor Suppressor Proteins genetics
- Abstract
Variants in the gene encoding the DLG5 scaffolding protein have been reported to be associated with increased risk of inflammatory bowel disease (IBD) and particularly Crohn's disease (Crohn disease; CD). These findings have not been uniformly replicated in follow-up studies. In this study we genotyped a cohort of 402 Canadian CD and 179 ulcerative colitis (UC) patients and 537 healthy controls for three IBD/CD-associated DLG5 variants. Our data reveal that the common DLG5 haplotype (A), which was previously considered protective for IBD, is associated with modest increases in risk for IBD (P=0.02) and CD (P=0.04). The effects of haplotype copy number on risk for IBD were minor, with the odds ratio (ORs) being 1.37 for the heterozygous risk genotype and 1.7 for the homozygous risk genotype. While we were unable to replicate the proposed association between the DLG5 c.113G>A variant and IBD, an association of IBD (P=0.02) and CD (P=0.04) with the rarer c.4136C>A variant was replicated in this cohort. These associations were restricted to the non-Jewish subjects in this cohort and were not detected in the Ashkenazi Jewish population studied here. Within the non-Jewish group, no associations were detected between the DLG5 variants and specific phenotypic features, such as site of disease, and there was no evidence of epistasis between DLG5 and any of the CD-associated CARD15 or SLC22A4/A5 gene variants. Together, the results indicate a role for DLG5 variants in IBD susceptibility and suggest that further studies are warranted to evaluate this role in different IBD populations and to determine the functional pathways that couple DLG5 variants to IBD., ((c) 2006 Wiley-Liss, Inc.)
- Published
- 2006
- Full Text
- View/download PDF
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