Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:PDH
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AIM:To analyse the role of two common polymorphismsin genes coding for histamine metabolising enzymes asit relates to the risk to develop ulcerative colitis(UC)andthe clinical course of these patients.METHODS:A cohort of 229 unrelated patients withUC recruited from a single centre and 261 healthyvolunteers were analysed for the presence of Thr105Ileand His645Asp amino acid substitutions at histamineN-methyltransferase(HNMT)and diamine oxidase(ABP1)enzymes,respectively,by amplification-restriction proce-dures.All patients were phenotyped and followed up forat least 2 years(mean time 11 years).RESULTS:There were no significant differences in thedistribution of ABP1 alleles between ulcerative colitispatients and healthy individuals[OR(95% CI)for vari-ant alleles=1.22(0.91-1.61)].However,mutated ABP1alleles were present with higher frequency among the58 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 ofABP1 versus HNMT on local histamine metabolism in hu-man bowel,the frequencies for carriers of HNMT geno-types or mutated alleles were similar among patients, regardless clinical evolution,and control individuals.CONCLUSION:The His645Asp polymorphism of thehistamine metabolising enzyme ABP1 is related to severityof ulcerative colitis. AIM: To analyze the role of two common polymorphisms in genes coding for histamine metabolising enzymes as the subject 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 center and 261 healthy volunteers were analyzed for the presence of ThrlOlI and His645Asp amino acid substitutions at histamine N-methyltransferase (HNMT) and diamine oxidase (ABPl) enzymes, respectively, by amplification-restriction proce dures. All patients were phenotyped and followed up forat least 2 years mean time 11 years .RESULTS: There were no significant differences in the distribution of ABP1 alleles between ulcerative colitispatients and healthy individuals [OR (95% CI) for vari-ant alleles = 1.22 (0.91-1.61)]. However, mutated ABP1alleles 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 hu-man bowel, the frequencies for carriers of HNMT geno-types or mutated alleles were similar among patients, regardless of clinical evolution, and control individuals.CONCLUSION: The His645Asp polymorphism of thehistamine metabolising enzyme ABP1 is related to severity of ulcerative colitis.
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