Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene

doi:10.3748/wjg.v12.i4.615

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Jan 28, 2006 (publication date) through Nov 24, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jan 28, 2006; 12(4): 615-620
Published online Jan 28, 2006. doi: 10.3748/wjg.v12.i4.615

Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene

Elena García-Martín, Juan L Mendoza, Carmen Martínez, Carlos Taxonera, Elena Urcelay, José M Ladero, Emilio G de la Concha, Manuel Díaz-Rubio, José AG Agúndez

Elena García-Martín, Department of Biochemistry & Molecular Biology & Genetics, University of Extremadura, Badajoz, Spain

Juan L Mendoza, Carlos Taxonera, José M Ladero, Manuel Díaz-Rubio, Service of Gastroenterology, Hospital Clínico San Carlos, Complutense University, Madrid, Spain

Carmen Martínez, José AG Agúndez, Department of Pharmacology, University of Extremadura, Badajoz, Spain

Elena Urcelay, Emilio G de la Concha, Service of Immunology, Hospital Clínico San Carlos, Complutense University, Madrid, Spain

Supported by Grants SAF 2003-00967 from Ministerio de Ciencia y Tecnología and FIS 02/0255 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain

Correspondence to: Professor José AG Agúndez. Department of Pharmacology, Medical School, University of Extremadura, Avda de Elvas s/n, E-06071, Badajoz, Spain. jagundez@unex.es

Telephone: +34924289458 Fax: +34924289676

Received: May 6, 2005
Revised: June 8, 2005
Accepted: June 18, 2005
Published online: January 28, 2006

Abstract

AIM: To analyse the role of two common polymorphisms in genes coding for histamine metabolising enzymes as it relates to the risk to develop ulcerative colitis (UC) and the clinical course of these patients.

METHODS: A cohort of 229 unrelated patients with UC recruited from a single centre and 261 healthy volunteers were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N-methyltransferase (HNMT) and diamine oxidase (ABP1) enzymes, respectively, by amplification-restriction procedures. All patients were phenotyped and followed up for at least 2 years (mean time 11 years).

RESULTS: There were no significant differences in the distribution of ABP1 alleles between ulcerative colitis patients and healthy individuals [OR (95% CI) for variant alleles = 1.22 (0.91-1.61)]. However, mutated ABP1 alleles were present with higher frequency among the 58 patients that required immunosuppresive drugs [OR (95 % CI) for carriers of mutated alleles 2.41 (1.21-4.83; P = 0.006)], with a significant gene-dose effect (P = 0.0038). In agreement with the predominant role of ABP1 versus HNMT on local histamine metabolism in human bowel, the frequencies for carriers of HNMT genotypes or mutated alleles were similar among patients, regardless clinical evolution, and control individuals.

CONCLUSION: The His645Asp polymorphism of the histamine metabolising enzyme ABP1 is related to severity of ulcerative colitis.

Keywords: Ulcerative colitis; Pharmacogenetics; Histamine N-Methyltransferase; Diamine Oxidase