血浆同型半胱氨酸及其代谢酶基因多态性与溃疡性结肠炎的相关性研究

目的 探讨血浆同型半胱氨酸(Hcy)、叶酸和维生素B12水平及Hcy代谢酶基因多态性与溃疡性结肠炎(UC)的关系.方法 收集310例UC患者和936名正常对照者,采用聚合酶链反应-限制性片断长度多态性(PCR-RELP)法检测亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C、甲硫氨酸合成酶(MTR) A2756G和甲硫氨酸合成还原酶(MTRR) A66G基因多态性;并从中随机选取88例UC患者和100名正常对照者,采用循环酶法检测血浆Hcy水平,微粒子免疫化学发光法检测叶酸和维生素B12浓度.结果 UC患者MTHFR A1298C、MTR A2756G和MTRRA66G突变的等位基因及基因型频率均明显增高(P值均<0.01).UC患者Hcy平均水平为(21.73±6.59)mmol/L,较正常对照组显著增高[(12.47±5.01)mmol/L,P<0.01],而叶酸和维生素B12平均水平分别为(11.25±6.19)nmol/L和(322.81±128.47)pmol/L,明显较正常对照组降低[(15.28±7.72)nmol/L和(422.59±129.36)pmol/L,P值均<0.01].Logistic回归分析提示血浆Hcy、叶酸和维生素B12浓度是UC的独立危险因素(P值均<0.01).结论 Hcy代谢酶基因多态性及血浆Hcy、叶酸和维生素B12水平异常与UC明显相关,为临床采用叶酸、维生素B12补充疗法治疗UC提供了理论依据.

Association of plasma homocysteine and gene polymorphisms of homocysteine with ulcerative colitis

Objective To evaluate association of plasma levels of homocysteine, folate and vitamin B12 as well as genetic polymorphisms of homocysteine with ulcerative colitis (UC). Methods Three hundred and ten consecutive patients with UC and 936 healthy controls were recruited.Polymorphisms of methylenetetrahyrdofolate reductase (MTHFR, C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G were genotyped using PCR-RELP methods. Eighty eight patients and one hundred healthy controls were randomly selected for determination of plasma levels of homocysteine by enzymatic cycling assay, and concentrations of folate and vitamin B12 were measured by corpuscle immune chemiluminescence assay. Results The variant allele and genotype frequencies of MTHFR 1298C, MTR 2756G and MTRR 66G were significantly higher in UC patients than in the healthy controls (P＜0. 01). Moreover, plasma homocysteine level was obviously higher in UC patients than in controls [(21.73±6.59) mmol/L vs(12.47±5.01)mmol/L,P<0.01).Whereas both folate F(11.25±6.19)nmol/L] and vitamin B12 [(322.81±128.47)pmol/L] concentrations were significantly lower in UC patients than in controls [(15.28±7.72)nmol/L and (422.59±129.36)pmol/L,respectively,P<0.01].Logistic analysis revealed that abnormal levels of homocysteine,folate and vitamin B12 were independent risk factors for UC(P<0.01).Conclusions Plasma levels of homocysteine,folate and vitamin B12 as well as the related genetic polymorphisms of homocystein are correlated with UC,which provides a theoretical basis for supplement of folate and vitamin B12 in treatment of UC patients.