Shula Nesher

Publications (6)16.65 Total impact

• Article: Granulomas in Crohn's disease: are newly discovered genetic variants involved?

  Yoav Mazor, Amir Karban, Shula Nesher, Batia Weiss, Esther Leshinsky-Silver, Arie Levine, Rami Eliakim
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  ABSTRACT: Non-caseating granulomas exist in a substantial portion of patients with Crohn's disease (CD). Several single nucleotide polymorphisms (SNPs) have been identified as a having strong association with CD, including SNPs within the autophagy related 4 homolog A (ATG4A) gene and the neutrophil cytosolic factor 4 (NCF4) gene. We hypothesized a possible association between the presence of granulomas in CD patients and variants in the ATG4A and NCF4 genes. To investigate whether variants in the NCF4 and ATG4A genes are associated with granuloma formation in a cohort of Israeli patients with CD, exploring demographic and clinical characteristics that differ between granuloma positive and granuloma negative patients. 307 Israeli patients with CD were studied. Patients with CD who underwent biopsy or resection of the intestine were classified according to presence or absence of granulomas. Using PCR-RFLP we determined the allele frequency in SNP rs4821544 (NCF4 gene) and SNP rs807185 (ATG4A gene) for all patients. Granulomas were found in 85 out of 307 CD patients (27%). There were no significant differences between patients with or without granulomas in allele frequency in SNPs rs4821544 and rs807185. CD Patients with granuloma were younger at diagnosis than patients without granuloma (mean age 19 vs. 27, respectively, P<0.0001) and were more likely to undergo surgery (55.3% vs. 34.8%, respectively, P=0.002). No association was found between SNPs rs4821544 and rs807185 and the presence of granulomas in CD patients. Granuloma positive patients were more likely to be younger and to undergo surgery.
  Journal of Crohn s and Colitis 10/2010; 4(4):438-43. · 2.57 Impact Factor
• Article: The association of Haptoglobin polymorphism with Crohn's disease in Israel.

  Itay Maza, Rachel Miller-Lotan, Andrew P Levy, Shula Nesher, Amir Karban, Rami Eliakim
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  ABSTRACT: Haptoglobin is a α(2)-sialoglycoprotein with hemoglobin binding capacity. Functional differences between the Hp phenotypes with the Hp 1-1 protein being a superior anti-inflammatory to the Hp 2-2 protein have been identified. The aim of our study was to investigate the possible role of Hp polymorphism in the susceptibility to Crohn's disease and its clinical course. Hp phenotypes were determined for 382 Israeli CD patients and 3243 healthy controls. Phenotypic data for all Crohn's disease patients were carefully characterized. Analysis was preformed to evaluate the association between Hp polymorphism and Crohn's disease. The frequency of Haptoglobin 1-1 was lower in Crohn's disease patients than in healthy individuals (6.28% vs. 9.28%, P=0.057). There was no association between Haptoglobin phenotypes and disease location, behavior or extra-intestinal manifestations. No association was found between the Haptoglobin polymorphism and the frequency of the three Crohn's disease associated NOD2 mutations examined. We found a borderline significant decrease of the Haptoglobin 1-1 phenotype in Israeli Crohn's disease patients compared to healthy controls. Our findings may support the importance of inflammation in Crohn's disease pathogenesis and the protective function of Haptoglobin 1-1 in the susceptibility for Crohn's disease.
  Journal of Crohn s and Colitis 09/2008; 2(3):214-8. · 2.57 Impact Factor
• Article: Paraoxonase (PON)1 192R allele carriage is associated with reduced risk of inflammatory bowel disease.

  Amir Karban, Corina Hartman, Rami Eliakim, Matti Waterman, Shula Nesher, Ofra Barnett-Griness, Raanan Shamir
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  ABSTRACT: The paraoxonase (PON) genes family maps to chromosome 7q21-q22, within a loci that also showed evidence of susceptibility genes for both Crohn's disease (CD) and ulcerative colitis (UC). In this case-control study we investigated the possible relationship between PON1 and PON2 polymorphisms and the risk of inflammatory bowel disease (IBD). PON1 192Q/R, PON1 55L/M, and PON2 311S/C polymorphisms were investigated by RFLP analysis in DNA samples from 224 patients with CD, 58 patients with UC, and 311 healthy controls. The PON1 192R allele was significantly less common among IBD Ashkenazi patients (allelic OR = 0.61, P = 0.004, 95% CI = 0.44-0.85). In agreement with the individual SNP analysis, Ashkenazi IBD patients had a higher frequency of haplotype PON1 192Q/PON1 55L/PON2 311S (26.3% vs 17.3%; P=0.003) and a lower frequency of haplotype PON1 192R/PON1 55L/PON2 311S (18.9% vs 27.7%; P=0.008). Our results suggest that in this Ashkenazi Jewish population, carriage of PON1 R192 allele may confer protection against the development of IBD.
  Digestive Diseases and Sciences 11/2007; 52(10):2707-15. · 2.12 Impact Factor
• Article: [The significance of IL-13 gene +2044G/A mutation in patients with inflammatory bowel disease].

  Matti Waterman, Amir Karban, Shula Nesher, Batia Weiss, Raanan Shamir, Rami Eliakim
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  ABSTRACT: Inflammatory bowel disease (IBD) is caused by a combination of genetic, immunological and environmental factors. Despite recent advances in the study of IBD pathogenesis, including the discovery of the NOD2/CARD15 mutation in 40% of Crohn's Disease (CD) patients, in most IBD patients no known mutations have yet been discovered. The interleukin (IL)-13 gene is located near the IBD5 locus on chromosome 5q31, known to be in linkage disequilibrium with CD. IL-13 has a role in the pathogenesis of several chronic inflammatory diseases including IBD. The +2044G/A mutation, which encodes an IL-13 protein with glutamine instead of arginine, has been associated with various inflammatory conditions. However, its role in IBD has not been defined. This is a study of the role of the IL-13 gene +2044G/A mutation in the susceptibility to and phenotype of IBD. Two hundred and eighty-five patients with CD and 111 cases of ulcerative colitis (UC) were enrolled in the study. Mutation frequency was determined using restriction fragment length polymorphism study in IBD patients and 178 healthy ethnically matched controls. The mutated allele frequency was determined in various clinical sub-groups of IBD patients. Statistical significance of the differences in allele frequency in CD and UC patients and healthy controls was determined. The +2044G/A allele frequency was similar in CD, UC and healthy controls (23.3%, 19.4%, 19.6%, respectively, p = 0.294). There was no significant association of +2044G/A mutation carriage with specific phenotypes of CD and UC. The IL-13 gene +2044G/A mutation has no significant role in susceptibility to and phenotype of IBD.
  Harefuah 12/2006; 145(11):789-92, 864.
• Article: The relation between NOD2/CARD15 mutations and the prevalence and phenotypic heterogeneity of Crohn's disease: lessons from the Israeli Arab Crohn's disease cohort.

  Amir Karban, Oren Atia, Eran Leitersdorf, Azmi Shahbari, Wisam Sbeit, Zvi Ackerman, Rawia Mualem, Arie Levine, Shula Nesher, Rifaat Safadi, Rami Eliakim
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  ABSTRACT: The prevalence of Crohn's disease depends on geographic location and racial background. Arg702Trp, Gly908Arg, and Leu1007fsinsC mutations in the NOD2/CARD15 gene are associated with Crohn's disease in Caucasians. The mutation rate among Israeli Jewish patients is 27%-41%. The prevalence of Crohn's disease is much lower in the Israeli Arab compared to the Israeli Jewish population. We studied the NOD2/CARD15 mutation rate and disease phenotype (according to the Vienna classification) among the Israeli Arabs and compared them with those in an Israeli Jewish cohort. We recruited 66 Israeli Arab patients and 122 ethnically matched controls. Five patients (8.2%) and three controls (2.3%) carried one NOD2/CARD15 mutation. The phenotypic characteristics of the Arab and Jewish patients were very similar. We conclude that NOD2/CARD15 mutations do not contribute to Crohn's susceptibility in the Israeli Arab population and suggest that NOD2/CARD15 mutations have an important effect on Crohn's prevalence within a specific population but not on the phenotype.
  Digestive Diseases and Sciences 10/2005; 50(9):1692-7. · 2.12 Impact Factor
• Article: NOD2/CARD15 genotype and phenotype differences between Ashkenazi and Sephardic Jews with Crohn's disease.

  Amir Karban, Matti Waterman, Carolien I Panhuysen, Rivka Dresner Pollak, Shula Nesher, Lisa Datta, Batia Weiss, Alain Suissa, Raanan Shamir, Steven R Brant, Rami Eliakim
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  ABSTRACT: NOD2/CARD15 has been identified as a major susceptibility gene for Crohn's disease (CD). Three mutations, Arg702Trp, Gly908Arg, and Leu1007fsinsC, are associated with CD. The incidence and prevalence rate of inflammatory bowel diseases is two- to four-fold higher in Ashkenazi Jews as compared to non-Jewish Caucasians. The aim of this study was to determine the significance of the NOD2/CARD15 mutations in Jewish CD patients in Israel, and more specifically, to compare the significance of the mutations to the expression of CD in the Ashkenazi and Sephardic Jewish populations. Allele frequencies of the mutations were determined in 180 Jewish CD patients, 73 ulcerative colitis patients, and 159 ethnically matched controls. Variants were detected using allele-specific PCR and restriction enzyme digestion assay. Demographic and phenotypic characterizations of the CD patients were determined. The carrier rate of the three mutations in the entire Jewish Israeli CD cohort is 41.1% versus 10.7% in controls (p < 0.0001). The Ashkenazi Jewish CD patients have an increased carrier rate compared to Sephardic Jews (47.4%vs 27.45%, p= 0.034). Association analyses in Ashkenazi Jews reveal odds ratios of 10.5, 9, and 4.8 for carriage of Gly908Arg, Arg702Trp, and Leu1007fsinsC mutations, respectively. Significantly higher rates of smoking, family history of inflammatory bowel diseases, and extraintestinal manifestations were found among the Sephardic CD patients. NOD2/CARD15 CD-associated mutations confer increased risk mainly to the Ashkenazi Jewish CD patients in Israel. This suggests that NOD2/CARD15 mutations could contribute to the higher incidence and prevalence rates of CD among Ashkenazi Jews.
  The American Journal of Gastroenterology 06/2004; 99(6):1134-40. · 7.28 Impact Factor