Devendra K. Amre PhD

Publications (5)24.28 Total impact

• Article: NELL1, NCF4, and FAM92B genes are not major susceptibility genes for Crohn's disease in canadian children and young adults

  Devendra K. Amre PhD, David R. Mack MD, David Israel MD, Alfreda Krupoves MD, Irina Costea PhD, Philippe Lambrette MSc, Guy Grimard MD, Jinsong Dong BSc, Emile Levy PhD
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  ABSTRACT: Background:Genome-wide association studies (GWAS) and replication studies have shown conflicting associations between the NELL1, NCF4, and FAM92B genes and susceptibility for Crohn's disease (CD). We sought to examine whether these genes were associated with CD in Canadian children and young adults.Methods:A case-control study was carried out at three pediatric gastroenterology clinics across Canada. Patients, ≤20 years at diagnosis, along with controls representative of the general population were selected. Study subjects were genotyped for 22 single nucleotide polymorphisms (SNPs) across the target genes. Allelic and haplotype associations were examined. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated.Results:In all, 566 CD cases and 602 controls were investigated. The mean (±SD) age of the patients was 12.3 (±3.3) years. Most patients were male (57.8%), of Caucasian ancestry (98.2%), and had ileocolonic disease location (48.8%). Barring nominal associations with one FAM92B SNP, none of the other 21 SNPs analyzed were associated with CD either at the allelic or haplotype level. Separate analysis for ileal CD (L1 plus L3) also did not reveal significant associations with any of the SNPs. Similarly, a pooled analysis using data from two recent studies did not demonstrate associations between the NCF4 (OR = 1.10, 95% CI = 0.91–1.32, P = 0.32) and FAM92B (OR = 1.05, 95% CI = 0.95–1.17, P = 0.36) GWAS lead SNPs and ileal CD.Conclusions:GWAS-reported associations in the NELL1, NCF4, and FAM92B genes could not be replicated in Canadian children and young adults. Further investigation in other populations will be required to confirm the presence/absence of associations, if any. (Inflamm Bowel Dis 2012;)
  Inflammatory Bowel Diseases 04/2011; 18(3):529 - 535. · 4.86 Impact Factor
• Article: Associations between ABCB1/MDR1 gene polymorphisms and Crohn's disease: A gene‐wide study in a pediatric population

  Alfreda Krupoves MD, Ernest G. Seidman MD, David Mack MD, David Israel MD, Kenneth Morgan PhD, Philippe Lambrette MSc, Irina Costea MD, Colette Deslandres MD, Guy Grimard MD, Liliane Law BSc, Emile Levy PhD, Devendra K. Amre PhD
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  ABSTRACT: Background: Functional studies support the involvement of the MDR1 gene in the pathways leading to Crohn's disease (CD). Two common single nucleotide polymorphisms (SNPs), C3435T and G2677T/A, thought to alter the function of the corresponding P-glycoprotein, have shown inconsistent associations with CD. We investigated whether DNA variants in the MDR1 gene were associated with susceptibility for CD and specific phenotypes in children.Methods: A case–control study was conducted at 3 gastroenterology clinics across Canada. Children with CD and population- or hospital-based controls were included. CD cases were classified using the Montreal Classification. Thirteen tag-SNPs and the C3435T variant in the MDR1 gene were genotyped. Single-SNP allelic, genotype as well as gene-wide haplotype associations with CD and its phenotypes at diagnosis were assessed.Results: A total of 270 CD cases and 336 controls were studied. Most cases were male (56.3%), had disease location L3±L4 (58.1%), and an inflammatory phenotype B1±p (88.5%). Allelic association analysis revealed that SNP rs17327442 was significantly associated with overall susceptibility to CD (odds ratio [OR] = 0.72, 95% confidence interval [CI] = 0.50–0.99, P = 0.04) but this association did not withstand corrections for multiple testing (q-value = 0.56). Genotype–phenotype analysis indicated that 2 SNPs (rs10248420, P = 0.007, q-value = 0.07; rs2032583, P = 0.01, q-value = 0.07) were significantly associated with colonic disease. Five SNPs, rs1128503 (P = 0.02), rs1202184 (P = 0.008), rs1202186 (P = 0.02), rs2091766 (P = 0.03), and rs2235046 (P = 0.03) were nominally associated with noninflammatory CD. Specific haplotypes comprising of the tag-SNPs were significantly associated with either colonic or noninflammatory CD.Conclusions: Our comprehensive gene-wide analysis suggests that the MDR1 gene may be associated with clinical phenotypes of CD in children.(Inflamm Bowel Dis 2008)
  Inflammatory Bowel Diseases 05/2009; 15(6):900 - 908. · 4.86 Impact Factor
• Article: Autophagy gene ATG16L1 but not IRGM is associated with Crohn's disease in Canadian children

  Devendra K. Amre PhD, David R. Mack MD, Kenneth Morgan PhD, Alfreda Krupoves MD, Irina Costea MD, Philippe Lambrette MSc, Guy Grimard MD, Jinsong Dong BSc, Houda Feguery MSc, Vytautas Bucionis MD, Colette Deslandres MD, Emile Levy PhD, Ernest G. Seidman MD
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  ABSTRACT: Background: Recent genome-wide studies have implicated the autophagy genes ATG16L1 and IRGM in the pathogenesis of Crohn's disease (CD). We investigated whether these genes were associated with CD in Canadian children.Methods: A case-control study was carried out at 2 pediatric gastroenterology clinics in Canada. Confirmed cases of CD <20 years diagnosed using standard criteria were classified according to the Montreal Classification scheme. Single nucleotide polymorphisms (SNPs) rs2241880 (ATG16L1) and rs10065172 (IRGM) along with CARD15 SNPs, SNP8, SNP12, and SNP13 were genotyped.Results: A total of 289 CD cases and 290 controls were studied. The mean age (±SD) of the cases was 12.1 (±3.5) years of age. Most cases were male (55.4%), had disease location L3 ± L4 (56.7%), and an inflammatory phenotype B1 ± p (87.2%) at diagnosis. rs2241880 (ATG16L1) was strongly associated with CD (allelic P = 1.24 × 10−6). Children with GG genotype had a more than 3-fold elevated risk for disease as compared to the wildtype AA homozygotes (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.93–4.94; P = 1.8 × 10−6). Association with SNP rs2241880 was specific for ileal disease (with or without colonic involvement) (case-based allelic P = 0.02; P-value versus controls = 9.5 × 10−8). The frequency of IRGM SNP rs10065172 was higher in cases but differences with controls were not statistically significant. No interactions between CARD15 and either ATG16L1 or IRGM were evident.Conclusions: We have confirmed associations between CD and ATG16L1 in a pediatric cohort of Canadian children. Associations with IRGM need to be further evaluated in larger studies.(Inflamm Bowel Dis 2008)
  Inflammatory Bowel Diseases 03/2009; 15(4):501 - 507. · 4.86 Impact Factor
• Article: Investigation of associations between the pregnane‐X receptor gene (NR1I2) and Crohn's disease in Canadian children using a gene‐wide haplotype‐based approach

  Devendra K. Amre PhD, David R. Mack MD, David Israel MD, Kenneth Morgan MSc, Alfreda Krupoves MD, Irina Costea MD, Philippe Lambrette, MSc Guy Grimard MD, Colette Deslandres MD, Emile Levy PhD, Ernest G. Seidman MD
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  ABSTRACT: Background: The pregnane-X-receptor (PXR) is involved in the metabolism and detoxification of numerous xenobiotics and is critical for maintaining intestinal integrity. The NR1I2 gene encoding PXR may confer susceptibility for Crohn's disease (CD) but evidence for associations is conflicting. We investigated whether the NR1I2 gene was associated with susceptibility for pediatric CD.Methods: A case-control and family-based (case-parent) study was carried out at 3 inflammatory bowel disease (IBD) clinics across Canada. Confirmed cases of CD <20 years were diagnosed using standard criteria. For determination of gene associations parents of the cases and unrelated controls were evaluated. Clinical phenotypes were established based on the Montreal Classification scheme. Eight tag-SNPs (tag-single nucleotide polymorphisms) across the gene were genotyped for allelic or genotypic associations.Results: A total of 270 CD cases, 336 controls, and 395 parents were studied. The mean age (±SD) of the cases was 12.1 (±3.5) years of age. Most cases were male (56.3%), had disease location L3±L4 (58.1%), and an inflammatory phenotype B1±p (88.4%) at diagnosis. For 7 SNPs single SNP analysis using case–control or case–parent data did not reveal associations with development of CD and none of the SNPs were significantly associated with disease location or disease behavior at diagnosis. One SNP rs2461823 (P = 0.05) was nominally associated with CD. No overall haplotype association (omnibus P-value = 0.61) or associations with individual haplotypes was evident.Conclusions: Our gene-wide analysis in a pediatric cohort using both the case–control and case–parent designs suggests that the NR1I2 gene is not associated with CD in Canadian children.(Inflamm Bowel Dis 2008)
  Inflammatory Bowel Diseases 03/2008; 14(9):1214 - 1218. · 4.86 Impact Factor
• Article: Dietary patterns and risk for Crohn's disease in children

  Savio D'Souza MBBS, Emile Levy PhD, David Mack MD, David Israel MD, Philippe Lambrette MSc, Parviz Ghadirian PhD, Colette Deslandres MD, Kenneth Morgan PhD, Ernest G. Seidman MD, Devendra K. Amre PhD
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  ABSTRACT: Background: Some dietary foods are considered protective (vegetables and fruits), whereas others (fatty foods) are thought to enhance the risk for Crohn's disease (CD). The evidence, however, is inconsistent.Methods: We postulated that specific dietary patterns may influence the risk for CD. A case-control study was carried out. Newly diagnosed CD cases with population and/or hospital-based controls ≤20 years were selected from 3 tertiary hospitals across Canada. Predisease diet was assessed using a validated food frequency questionnaire (FFQ) administered within 1 month of diagnosis. Factor analyses and unconditional logistic regression (adjusted) was used to determine gender-specific dietary patterns and assess associated risks for CD. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were estimated.Results: A total of 149 cases and 251 controls were included. The mean age (range) of the cases was 13.3 (2.6-20 years). There were more boys (61.1%). Four dietary patterns each were observed among both boys and girls. Pattern 1 in girls, characterized by meats, fatty foods, and desserts, was positively associated with CD (OR 4.7, 95% CI 1.6–14.2). Pattern 2, common to both boys and girls, was characterized by vegetables, fruits, olive oil, fish, grains, and nuts and was inversely associated with CD in both genders (girls: OR 0.3, 95% CI 0.1–0.9; boys: OR 0.2, 95% CI 0.1–0.5).Conclusions: Our results suggest that specific dietary patterns could be associated with higher or lower risks for CD in children. Larger prospective studies are required to confirm these findings.(Inflamm Bowel Dis 2007)
  Inflammatory Bowel Diseases 02/2008; 14(3):367 - 373. · 4.86 Impact Factor