Lower level of serum betaine is associated with an increased risk of microangiopathy in diabetics

BACKGROUND: Diabetes represents one of the greatest medical and socioeconomic emergencies worldwide and 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 aims to investigate 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.
METHODS: 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-mass spectrometry (HPLC-MS). Serum concentration of homocysteine was assayed using HPLC. PEMT gene mutations were detected by polymerase chain reaction and restriction fragment length polymorphism.
RESULTS: After adjustment for the 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).
CONCLUSION: The GG genotype of the PEMT G774C polymorphism, higher level of serum homocysteine, and lower level of serum betaine are associated with an increased risk of microangiopathy in patients with diabetes.

Chen, L., et al., Higher homocysteine and lower betaine increases the risk of microangiopathy in patients with diabetes mellitus carrying the GG genotype of PEMT G774C. Diabetes Metab Res Rev, 2013