Jiang Yi, Zhao Jie, Xu Chang-long, Cao Shu-guang, Lin Li-miao, Lei Yuan, Huang Sha, Wang Chang-gao, Xia Bing
Department of Gastroenterology, Wuhan University Zhongnan Hospital, Wuhan 430071, China.
Zhonghua Nei Ke Za Zhi. 2010 Aug;49(8):675-9.
The present study aimed to investigate the associations between genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) G1793A, plasma homocysteine (Hcy) levels, vitamin status and ulcerative colitis (UC) in a cohort of patients in Hubei Han nationality.
Two hundred and ninety-nine UC patients and 764 age- and sex-matched healthy controls were recruited in this study. Polymorphism of MTHFR G1793A was examined using a PCR-RELP method. Plasma levels of Hcy, folate and vitamin B12 were determined by enzymatic cycling assay and corpuscle immune chemiluminescence assay, respectively.
Both variant allele and genotype frequencies in MTHFR G1793A gene were significantly higher in the UC patients compared to the controls (22.24% vs 14.20%, P < 0.001; 42.81% vs 26.97%, P<0.001, respectively). Plasma Hcy levels were increased in UC patients compared to the controls [(20.67 ± 6.42) mmol/L vs (13.21±5.11) mmol/L, P<0.001] while folate and vitamin B12 concentrations were significantly decreased [(11.37±6.34) nmol/L vs (14.89±7.21) nmol/L, P<0.001; (324.15±127.53) pmol/L vs (421.54±128.45) pmol/L, P<0.001, respectively]. Furthermore, hyperhomocysteinaemia (HHcy) and folate deficiency were also more prevalent in the UC patients (32.44% vs 25.78%, P=0.029; 23.41% vs 17.01%, P=0.016, respectively).
Genetic polymorphism of MTHFR G1793A was strongly associated with UC. HHcy, folate deficiency and low vitamin B12 concentration were common phenomena in the UC patients of Hubei Han nationality. Our findings demonstrate that the genes related to Hcy metabolism may play an important role in the pathogenesis of UC.
本研究旨在调查湖北汉族患者队列中，亚甲基四氢叶酸还原酶（MTHFR）G1793A基因多态性、血浆同型半胱氨酸（Hcy）水平、维生素状态与溃疡性结肠炎（UC）之间的关联。
本研究招募了299例UC患者和764例年龄及性别匹配的健康对照。采用聚合酶链反应-限制性片段长度多态性（PCR-RELP）方法检测MTHFR G1793A基因多态性。分别采用酶循环法和血细胞免疫化学发光法测定血浆Hcy、叶酸和维生素B12水平。
与对照组相比，UC患者中MTHFR G1793A基因的变异等位基因频率和基因型频率均显著更高（分别为22.24%对14.20%，P<０.００１；42.81%对26.97%，P<０.００１）。与对照组相比，UC患者的血浆Hcy水平升高[（20.67±6.42）mmol/L对（13.21±5.11）mmol/L，P<０.００１]，而叶酸和维生素B12浓度显著降低[（11.37±6.34）nmol/L对（14.89±7.21）nmol/L，P<０.００１；（324.15±127.53）pmol/L对（421.54±128.45）pmol/L，P<０.００１]。此外，高同型半胱氨酸血症（HHcy）和叶酸缺乏在UC患者中也更普遍（分别为32.44%对25.78%，P=0.029；23.41%对17.01%，P=0.016）。
MTHFR G1793A基因多态性与UC密切相关。HHcy、叶酸缺乏和低维生素B12浓度在湖北汉族UC患者中是常见现象。我们的研究结果表明，与Hcy代谢相关的基因可能在UC的发病机制中起重要作用。
