Singh S, Choudhuri G, Kumar R, Agarwal S
Departments of Genetics and Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India.
Cell Mol Biol (Noisy-le-grand). 2012 Dec 22;58(1):122-7.
MTHFR is a key enzyme in folate metabolism that catalyzes the conversion of 5, 10—methlenetetrahydrofolate (5, 10— methylene THF) to 5—methyltetrahydrofolate (5—methyl THF), a predominant circulatory form of folate and methyl donor for the remethylation of homocysteine to methionine. Some studies have shown that C667T polymorphism increases the risk of pancreatic cancer. Since MTHFR is involved in methylation, inflammation and protection against oxidative stress, the processes especially important for pancreatic homeostasis. The altered enzyme activity could play a role in pancreatic injury. The role of MTHFR C677T polymorphism in chronic pancreatitis has been explored by conducting a hospital based; case—control study involving 100 patients radiologically confirmed chronic pancreatitis and 329 healthy controls. All samples were analyzed for MTHFR C677T polymorphism using PCR—RFLP method. Restriction enzyme Hinf I was used to digest the 198 bp amplified product. The frequency of the MTHFR was 57.3%, 34.1% and 8.5% among cases compared with 87.2%,11.2% and 1.5% of controls for CC, CT and TT genotypes, respectively. The T Allele frequency was found significantly higher in patients than in controls. A significant association with T allele was observed with p—value (< 0.0001) odds ratio 4.475 and (95% CI=2.961—7.046). It could be predisposing to the traditional risk factors such as diabetes, dietary, alcohal and smoking habit that are known to be associated with chronic pancreatitis. Additionally it was observed that smoking increases the risk of chronic pancreatitis by 4.1 times. The T allele frequency of MTHFR (C667T) was found to be a significant risk factor for chronic pancreatitis playing a crucial role in altered folate metabolsim.
亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢中的一种关键酶，它催化5,10-亚甲基四氢叶酸（5,10-亚甲基THF）转化为5-甲基四氢叶酸（5-甲基THF），5-甲基THF是叶酸的主要循环形式，也是同型半胱氨酸再甲基化为蛋氨酸的甲基供体。一些研究表明，C667T多态性会增加患胰腺癌的风险。由于MTHFR参与甲基化、炎症反应以及抗氧化应激保护，这些过程对胰腺内环境稳定尤为重要。酶活性的改变可能在胰腺损伤中起作用。通过开展一项基于医院的病例对照研究，探讨了MTHFR C677T多态性在慢性胰腺炎中的作用，该研究纳入了100例经放射学确诊的慢性胰腺炎患者和329例健康对照。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对所有样本进行MTHFR C677T多态性分析。使用限制性内切酶Hinf I消化198 bp的扩增产物。CC、CT和TT基因型在病例组中的频率分别为57.3%、34.1%和8.5%，而在对照组中分别为87.2%、11.2%和1.5%。发现患者中T等位基因频率显著高于对照组。观察到T等位基因与p值（<0.0001）、优势比4.475以及（95%置信区间=2.961-7.046）存在显著关联。它可能易患已知与慢性胰腺炎相关的传统危险因素，如糖尿病、饮食、酒精和吸烟习惯。此外，观察到吸烟会使慢性胰腺炎的风险增加4.1倍。发现MTHFR（C667T）的T等位基因频率是慢性胰腺炎的一个重要危险因素，在叶酸代谢改变中起关键作用。
