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


CONCLUSIONS
The His645Asp polymorphism of the histamine metabolising enzyme ABP1 is related to severity of ulcerative colitis.
Department of Pharmacology, Medical School, University of Extremadura, Avda de Elvas s/n, E-06071 Badajoz, Spain.
Elena
E
García-Martin
Juan L
JL
Mendoza
Carmen
C
Martínez
Carlos
C
Taxonera
Elena
E
Urcelay
José M
JM
Ladero
Emilio G
EG
de la Concha
Manuel
M
Díaz-Rubio
José A G
JA
Agúndez
D000328:Adult; D000368:Aged; D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics*; D005260:Female; D005838:Genotype; D006637:Histamine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
D002352:Carrier Proteins; D006631:Amine Oxidase (Copper-Containing); C065976:AOC1 protein, human; D006637:Histamine N-Methyltransferase