Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.
Diabetes Metab Res Rev. 2013 Nov;29(8):607-17. doi: 10.1002/dmrr.2432.
Diabetes represents one of the greatest medical and socioeconomic threats worldwide. The pathogenesis involved is complicated. The effect of methyl donors and genetic polymorphisms in metabolic enzymes on the risk of microangiopathy in patients with diabetes is not well understood. This study investigates the association of homocysteine, choline and betaine levels and phosphatidylethanolamine N-methyltransferase (PEMT) G774C (rs12325817) genotypes with the risk of diabetes and its related microangiopathic complications.
Between January 2009 and June 2010, 184 diabetic patients and 188 non-diabetic control subjects were enrolled in the hospital-based case-control study. Serum concentrations of betaine and choline were determined by high-performance liquid chromatography (HPLC)-mass spectrometry. Serum concentrations of homocysteine were assayed using HPLC. PEMT gene mutations were detected by polymerase chain reaction and restriction fragment length polymorphism.
After adjustment for potential confounders, serum total homocysteine had a significant dose-dependent positive association, and serum choline had an inverse association with the risks of diabetes and its microangiopathic complications (both p < 0.001). Although serum betaine was not associated with the risk of diabetes, it had a significant inverse association with diabetic microangiopathy. Compared with GG genotype, the CC genotype of PEMT G774C was associated with a decreased risk of diabetes (OR 0.559, 95% CI 0.338, 0.926) and its microangiopathy (OR 0.452, 95% CI 0.218, 0.937).
The GG genotype of the PEMT G774C polymorphism, higher levels of serum homocysteine and lower levels of serum betaine are associated with an increased risk of microangiopathy in patients with diabetes.
糖尿病是全球面临的最大医学和社会经济威胁之一。其发病机制复杂。关于甲硫氨酸供体和代谢酶的遗传多态性对糖尿病患者发生微血管病变风险的影响，目前还知之甚少。本研究旨在探讨同型半胱氨酸、胆碱和甜菜碱水平与磷脂乙醇胺 N-甲基转移酶（PEMT）G774C（rs12325817）基因型与糖尿病及其相关微血管并发症风险的关系。
本病例对照研究于 2009 年 1 月至 2010 年 6 月在医院进行，共纳入 184 例糖尿病患者和 188 例非糖尿病对照者。采用高效液相色谱-质谱法（HPLC-MS）测定甜菜碱和胆碱的血清浓度。采用 HPLC 法测定同型半胱氨酸的血清浓度。通过聚合酶链反应和限制性片段长度多态性检测 PEMT 基因突变。
校正潜在混杂因素后，血清总同型半胱氨酸与糖尿病及其微血管并发症的风险呈显著剂量依赖性正相关，血清胆碱与糖尿病及其微血管并发症的风险呈负相关（均 P<0.001）。虽然血清甜菜碱与糖尿病的发病风险无关，但与糖尿病性微血管病变呈显著负相关。与 GG 基因型相比，PEMT G774C 的 CC 基因型与糖尿病的发病风险降低相关（OR 0.559，95%CI 0.338，0.926）及其微血管病变（OR 0.452，95%CI 0.218，0.937）。
PEMT G774C 多态性的 GG 基因型、较高的血清同型半胱氨酸水平和较低的血清甜菜碱水平与糖尿病患者微血管病变风险增加相关。
