Skip to main content
Erschienen in: International Journal of Colorectal Disease 5/2009

01.05.2009 | Original Article

IGR2096a_1 T and IGR2198a_1 C alleles on IBD5 locus of chromosome 5q31 region confer risk for Crohn’s disease in Hungarian patients

verfasst von: Lilla Lakner, Veronika Csöngei, Patrícia Sarlós, Luca Járomi, Enikő Sáfrány, Márta Varga, Péter Orosz, Lili Magyari, Judit Bene, Pál Miheller, Zsolt Tulassay, Béla Melegh

Erschienen in: International Journal of Colorectal Disease | Ausgabe 5/2009

Einloggen, um Zugang zu erhalten

Abstract

Background and aims

We investigated the possible association of IBD with C1672T of SLC22A4 and G-207C of SLC22A5 alleles, and with the novel IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility loci, all located on IBD5 locus of chromosome 5q31.

Materials and methods

DNA of 217 Crohn’s disease, 252 ulcerative colitis, and 290 control patients were analyzed by polymerase chain reaction/restriction fragment length polymorphism methods.

Results

Neither the C1672T and G-207C alleles, nor the TC haplotype were found to be risk factors. By contrast, the minor allele frequencies of IGR2096a_1 T (47.2%) and IGR2198a_1 C (45.9%) were increased in Crohn’s disease compared with the controls (38.2% and 37.7%, respectively; p < 0.05); multivariate regression analysis revealed a risk nature for Crohn’s disease (OR = 1.748, 95% CI 1.186–2.574; p = 0.007 for T allele, OR = 1.646, 95% CI 1.119–2.423, p = 0.011 for C allele of IGRs).

Conclusion

The data suggest a special haplotype arrangement of susceptibility genes at the IBD5 locus in Hungarians, which nation differs historically from the surrounding Caucasian ethnicities in its origin.
Literatur
2.
Zurück zum Zitat Weersma RK, van Dullemen HM, van der SG et al (2007) Review article: inflammatory bowel disease and genetics. Aliment Pharmacol Ther 26 Suppl 2:57–65 Weersma RK, van Dullemen HM, van der SG et al (2007) Review article: inflammatory bowel disease and genetics. Aliment Pharmacol Ther 26 Suppl 2:57–65
3.
Zurück zum Zitat Karban AEliakim R (2007) Effect of smoking on inflammatory bowel disease: is it disease or organ specific? World J Gastroenterol 13:2150–2152 Karban AEliakim R (2007) Effect of smoking on inflammatory bowel disease: is it disease or organ specific? World J Gastroenterol 13:2150–2152
4.
Zurück zum Zitat Lakatos PL, Szamosi T, Lakatos L (2007) Smoking in inflammatory bowel diseases: good, bad or ugly? World J Gastroenterol 13:6134–6139PubMedCrossRef Lakatos PL, Szamosi T, Lakatos L (2007) Smoking in inflammatory bowel diseases: good, bad or ugly? World J Gastroenterol 13:6134–6139PubMedCrossRef
5.
Zurück zum Zitat Ferguson LR, Shelling AN, Browning BL, Huebner C, Petermann I (2007) Genes, diet and inflammatory bowel disease. Mutat Res 622:70–83PubMed Ferguson LR, Shelling AN, Browning BL, Huebner C, Petermann I (2007) Genes, diet and inflammatory bowel disease. Mutat Res 622:70–83PubMed
6.
Zurück zum Zitat Rogala L, Miller N, Graff LA et al (2008) Population-based controlled study of social support, self-perceived stress, activity and work issues, and access to health care in inflammatory bowel disease. Inflamm Bowel Dis 14:526–535PubMedCrossRef Rogala L, Miller N, Graff LA et al (2008) Population-based controlled study of social support, self-perceived stress, activity and work issues, and access to health care in inflammatory bowel disease. Inflamm Bowel Dis 14:526–535PubMedCrossRef
7.
Zurück zum Zitat Jantchou P, Monnet E, Carbonnel F (2006) Environmental risk factors in Crohn’s disease and ulcerative colitis (excluding tobacco and appendicectomy). Gastroenterol Clin Biol 30:859–867PubMedCrossRef Jantchou P, Monnet E, Carbonnel F (2006) Environmental risk factors in Crohn’s disease and ulcerative colitis (excluding tobacco and appendicectomy). Gastroenterol Clin Biol 30:859–867PubMedCrossRef
8.
Zurück zum Zitat Siminovitch KA (2006) Advances in the molecular dissection of inflammatory bowel disease. Semin Immunol 18:244–253PubMedCrossRef Siminovitch KA (2006) Advances in the molecular dissection of inflammatory bowel disease. Semin Immunol 18:244–253PubMedCrossRef
9.
Zurück zum Zitat Rioux JD, Silverberg MS, Daly MJ et al (2000) Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am J Hum Genet 66:1863–1870PubMedCrossRef Rioux JD, Silverberg MS, Daly MJ et al (2000) Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am J Hum Genet 66:1863–1870PubMedCrossRef
10.
Zurück zum Zitat Ma Y, Ohmen JD, Li Z et al (1999) A genome-wide search identifies potential new susceptibility loci for Crohn’s disease. Inflamm Bowel Dis 5:271–278PubMed Ma Y, Ohmen JD, Li Z et al (1999) A genome-wide search identifies potential new susceptibility loci for Crohn’s disease. Inflamm Bowel Dis 5:271–278PubMed
11.
Zurück zum Zitat Peltekova VD, Wintle RF, Rubin LA et al (2004) Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 36:471–475PubMedCrossRef Peltekova VD, Wintle RF, Rubin LA et al (2004) Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 36:471–475PubMedCrossRef
12.
Zurück zum Zitat Silverberg MS, Duerr RH, Brant SR et al (2007) Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn’s disease. Eur J Hum Genet 15:328–335PubMedCrossRef Silverberg MS, Duerr RH, Brant SR et al (2007) Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn’s disease. Eur J Hum Genet 15:328–335PubMedCrossRef
13.
Zurück zum Zitat Sartor RB (2006) Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 3:390–407PubMedCrossRef Sartor RB (2006) Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 3:390–407PubMedCrossRef
14.
Zurück zum Zitat Crawford NP, Colliver DW, Funke AA et al (2005) Characterization of genotype-phenotype relationships and stratification by the CARD15 variant genotype for inflammatory bowel disease susceptibility loci using multiple short tandem repeat genetic markers. Hum Mutat 25:156–166PubMedCrossRef Crawford NP, Colliver DW, Funke AA et al (2005) Characterization of genotype-phenotype relationships and stratification by the CARD15 variant genotype for inflammatory bowel disease susceptibility loci using multiple short tandem repeat genetic markers. Hum Mutat 25:156–166PubMedCrossRef
15.
Zurück zum Zitat Buning C, Geerdts L, Fiedler T et al (2006) DLG5 variants in inflammatory bowel disease. Am J Gastroenterol 101:786–792PubMedCrossRef Buning C, Geerdts L, Fiedler T et al (2006) DLG5 variants in inflammatory bowel disease. Am J Gastroenterol 101:786–792PubMedCrossRef
16.
Zurück zum Zitat Cucchiara S, Latiano A, Palmieri O et al (2007) Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases. World J Gastroenterol 13:1221–1229PubMed Cucchiara S, Latiano A, Palmieri O et al (2007) Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases. World J Gastroenterol 13:1221–1229PubMed
17.
Zurück zum Zitat Ferraris A, Torres B, Knafelz D et al (2006) Relationship between CARD15, SLC22A4/5, and DLG5 polymorphisms and early-onset inflammatory bowel diseases: an Italian multicentric study. Inflamm Bowel Dis 12:355–361PubMedCrossRef Ferraris A, Torres B, Knafelz D et al (2006) Relationship between CARD15, SLC22A4/5, and DLG5 polymorphisms and early-onset inflammatory bowel diseases: an Italian multicentric study. Inflamm Bowel Dis 12:355–361PubMedCrossRef
18.
Zurück zum Zitat Glas J, Seiderer J, Wetzke M et al (2007) rs1004819 is the main disease-associated IL23R variant in German Crohn’s disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants. PLoS ONE2:e819 Glas J, Seiderer J, Wetzke M et al (2007) rs1004819 is the main disease-associated IL23R variant in German Crohn’s disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants. PLoS ONE2:e819
19.
Zurück zum Zitat Hampe J, Franke A, Rosenstiel P et al (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211PubMedCrossRef Hampe J, Franke A, Rosenstiel P et al (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211PubMedCrossRef
20.
Zurück zum Zitat Prescott NJ, Fisher SA, Franke A et al (2007) A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn’s disease and is independent of CARD15 and IBD5. Gastroenterology 132:1665–1671PubMedCrossRef Prescott NJ, Fisher SA, Franke A et al (2007) A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn’s disease and is independent of CARD15 and IBD5. Gastroenterology 132:1665–1671PubMedCrossRef
21.
Zurück zum Zitat Raelson JV, Little RD, Ruether A et al (2007) Genome-wide association study for Crohn’s disease in the Quebec Founder Population identifies multiple validated disease loci. Proc Natl Acad Sci U S A 104:14747–14752PubMedCrossRef Raelson JV, Little RD, Ruether A et al (2007) Genome-wide association study for Crohn’s disease in the Quebec Founder Population identifies multiple validated disease loci. Proc Natl Acad Sci U S A 104:14747–14752PubMedCrossRef
22.
Zurück zum Zitat Rioux JD, Xavier RJ, Taylor KD et al (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39:596–604PubMedCrossRef Rioux JD, Xavier RJ, Taylor KD et al (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39:596–604PubMedCrossRef
23.
Zurück zum Zitat Fisher SA, Hampe J, Onnie CM et al (2006) Direct or indirect association in a complex disease: the role of SLC22A4 and SLC22A5 functional variants in Crohn disease. Hum Mutat 27:778–785PubMedCrossRef Fisher SA, Hampe J, Onnie CM et al (2006) Direct or indirect association in a complex disease: the role of SLC22A4 and SLC22A5 functional variants in Crohn disease. Hum Mutat 27:778–785PubMedCrossRef
24.
Zurück zum Zitat Negoro K, McGovern DP, Kinouchi Y et al (2003) Analysis of the IBD5 locus and potential gene-gene interactions in Crohn’s disease. Gut 52:541–546PubMedCrossRef Negoro K, McGovern DP, Kinouchi Y et al (2003) Analysis of the IBD5 locus and potential gene-gene interactions in Crohn’s disease. Gut 52:541–546PubMedCrossRef
25.
Zurück zum Zitat Waller S, Tremelling M, Bredin F et al (2006) Evidence for association of OCTN genes and IBD5 with ulcerative colitis. Gut 55:809–814PubMedCrossRef Waller S, Tremelling M, Bredin F et al (2006) Evidence for association of OCTN genes and IBD5 with ulcerative colitis. Gut 55:809–814PubMedCrossRef
26.
Zurück zum Zitat Torok HP, Glas J, Tonenchi L et al (2005) Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn’s disease. Gut 54:1421–1427PubMedCrossRef Torok HP, Glas J, Tonenchi L et al (2005) Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn’s disease. Gut 54:1421–1427PubMedCrossRef
27.
Zurück zum Zitat Gazouli M, Mantzaris G, Archimandritis AJ, Nasioulas G, Anagnou NP (2005) Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn’s disease. World J Gastroenterol 11:7525–7530PubMed Gazouli M, Mantzaris G, Archimandritis AJ, Nasioulas G, Anagnou NP (2005) Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn’s disease. World J Gastroenterol 11:7525–7530PubMed
28.
Zurück zum Zitat Newman B, Gu X, Wintle R et al (2005) A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn’s disease. Gastroenterology 128:260–269PubMedCrossRef Newman B, Gu X, Wintle R et al (2005) A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn’s disease. Gastroenterology 128:260–269PubMedCrossRef
29.
Zurück zum Zitat Palmieri O, Latiano A, Valvano R et al (2006) Variants of OCTN1-2 cation transporter genes are associated with both Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther 23:497–506PubMedCrossRef Palmieri O, Latiano A, Valvano R et al (2006) Variants of OCTN1-2 cation transporter genes are associated with both Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther 23:497–506PubMedCrossRef
30.
Zurück zum Zitat Leung E, Hong J, Fraser AG et al (2006) Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn’s disease in a New Zealand Caucasian cohort. Immunol Cell Biol 84:233–236PubMedCrossRef Leung E, Hong J, Fraser AG et al (2006) Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn’s disease in a New Zealand Caucasian cohort. Immunol Cell Biol 84:233–236PubMedCrossRef
31.
Zurück zum Zitat Noble CL, Nimmo ER, Drummond H et al (2005) The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn’s disease. Gastroenterology 129:1854–1864PubMedCrossRef Noble CL, Nimmo ER, Drummond H et al (2005) The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn’s disease. Gastroenterology 129:1854–1864PubMedCrossRef
32.
Zurück zum Zitat Russell RK, Drummond HE, Nimmo ER et al (2006) Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease. Gut 55:1114–1123PubMedCrossRef Russell RK, Drummond HE, Nimmo ER et al (2006) Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease. Gut 55:1114–1123PubMedCrossRef
33.
Zurück zum Zitat Urcelay E, Mendoza JL, Martinez A et al (2005) IBD5 polymorphisms in inflammatory bowel disease: association with response to infliximab. World J Gastroenterol 11:1187–1192PubMed Urcelay E, Mendoza JL, Martinez A et al (2005) IBD5 polymorphisms in inflammatory bowel disease: association with response to infliximab. World J Gastroenterol 11:1187–1192PubMed
34.
Zurück zum Zitat Torkvist L, Noble CL, Lordal M et al (2007) Contribution of the IBD5 locus to Crohn’s disease in the Swedish population. Scand J Gastroenterol 42:200–206PubMedCrossRef Torkvist L, Noble CL, Lordal M et al (2007) Contribution of the IBD5 locus to Crohn’s disease in the Swedish population. Scand J Gastroenterol 42:200–206PubMedCrossRef
35.
Zurück zum Zitat Vermeire S, Pierik M, Hlavaty T et al (2005) Association of organic cation transporter risk haplotype with perianal penetrating Crohn’s disease but not with susceptibility to IBD. Gastroenterology 129:1845–1853PubMedCrossRef Vermeire S, Pierik M, Hlavaty T et al (2005) Association of organic cation transporter risk haplotype with perianal penetrating Crohn’s disease but not with susceptibility to IBD. Gastroenterology 129:1845–1853PubMedCrossRef
36.
Zurück zum Zitat Bene J, Magyari L, Talian G et al (2006) Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn’s disease. World J Gastroenterol 12:5550–5553PubMed Bene J, Magyari L, Talian G et al (2006) Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn’s disease. World J Gastroenterol 12:5550–5553PubMed
37.
Zurück zum Zitat Magyari L, Bene J, Komlosi K et al (2007) Prevalence of SLC22A4 1672T and SLC22A5 -207C combination defined TC haplotype in Hungarian ulcerative colitis patients. Pathol Oncol Res 13:53–56PubMedCrossRef Magyari L, Bene J, Komlosi K et al (2007) Prevalence of SLC22A4 1672T and SLC22A5 -207C combination defined TC haplotype in Hungarian ulcerative colitis patients. Pathol Oncol Res 13:53–56PubMedCrossRef
38.
Zurück zum Zitat Tosa M, Negoro K, Kinouchi Y et al (2006) Lack of association between IBD5 and Crohn’s disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease. Scand J Gastroenterol 41:48–53PubMedCrossRef Tosa M, Negoro K, Kinouchi Y et al (2006) Lack of association between IBD5 and Crohn’s disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease. Scand J Gastroenterol 41:48–53PubMedCrossRef
39.
Zurück zum Zitat Nadasi E, Gyurus P, Czako M et al (2007) Comparison of mtDNA haplogroups in Hungarians with four other European populations: a small incidence of descents with Asian origin. Acta Biol Hung 58:245–256PubMedCrossRef Nadasi E, Gyurus P, Czako M et al (2007) Comparison of mtDNA haplogroups in Hungarians with four other European populations: a small incidence of descents with Asian origin. Acta Biol Hung 58:245–256PubMedCrossRef
Metadaten
Titel
IGR2096a_1 T and IGR2198a_1 C alleles on IBD5 locus of chromosome 5q31 region confer risk for Crohn’s disease in Hungarian patients
verfasst von
Lilla Lakner
Veronika Csöngei
Patrícia Sarlós
Luca Járomi
Enikő Sáfrány
Márta Varga
Péter Orosz
Lili Magyari
Judit Bene
Pál Miheller
Zsolt Tulassay
Béla Melegh
Publikationsdatum
01.05.2009
Verlag
Springer-Verlag
Erschienen in
International Journal of Colorectal Disease / Ausgabe 5/2009
Print ISSN: 0179-1958
Elektronische ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-009-0670-x

Weitere Artikel der Ausgabe 5/2009

International Journal of Colorectal Disease 5/2009 Zur Ausgabe

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

28.05.2024 Häusliche Gewalt Nachrichten

In der Notaufnahme wird die Chance, Opfer von häuslicher Gewalt zu identifizieren, von Orthopäden und Orthopädinnen offenbar zu wenig genutzt. Darauf deuten die Ergebnisse einer Fragebogenstudie an der Sahlgrenska-Universität in Schweden hin.

Fehlerkultur in der Medizin – Offenheit zählt!

28.05.2024 Fehlerkultur Podcast

Darüber reden und aus Fehlern lernen, sollte das Motto in der Medizin lauten. Und zwar nicht nur im Sinne der Patientensicherheit. Eine negative Fehlerkultur kann auch die Behandelnden ernsthaft krank machen, warnt Prof. Dr. Reinhard Strametz. Ein Plädoyer und ein Leitfaden für den offenen Umgang mit kritischen Ereignissen in Medizin und Pflege.

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

TAVI versus Klappenchirurgie: Neue Vergleichsstudie sorgt für Erstaunen

21.05.2024 TAVI Nachrichten

Bei schwerer Aortenstenose und obstruktiver KHK empfehlen die Leitlinien derzeit eine chirurgische Kombi-Behandlung aus Klappenersatz plus Bypass-OP. Diese Empfehlung wird allerdings jetzt durch eine aktuelle Studie infrage gestellt – mit überraschender Deutlichkeit.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.