Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Diabetes Care. 2010 Mar;33(3):463-6. doi: 10.2337/dc09-1724. Epub 2009 Dec 10.
OBJECTIVE An association of the C-857T polymorphism of the tumor necrosis factor-alpha (TNF-alpha) gene promoter region with LDL cholesterol levels has been reported. This study was designed to evaluate the relationship between the TNF-alpha-C-857T polymorphism and LDL cholesterol levels according to statin treatment in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS DNA was obtained from 322 Japanese subjects (160 male and 162 female) with type 2 diabetes, and TNF-alpha-C-857T polymorphisms were determined by direct sequencing. Serum LDL cholesterol was measured by a direct method. RESULTS Although serum LDL cholesterol levels were significantly higher in the T carriers (C/T + T/T) than in the non-T carriers (C/C) (3.14 +/- 0.86 vs. 2.89 +/- 0.75 mmol/l, P < 0.05), there was no difference in LDL cholesterol levels between the non-T carriers and the T carriers in statin-untreated subjects (2.87 +/- 0.73 vs. 2.89 +/- 0.76 mmol/l, NS), whereas in statin-treated subjects, LDL cholesterol levels were significantly higher in the T carriers than in the non-T carriers (3.43 +/- 0.89 vs. 2.90 +/- 0.78 mmol/l, P = 0.0007). There were no differences in HDL cholesterol and triglyceride levels between the non-T carriers and the T carriers in both statin-treated and -untreated subjects. The percent decrease in LDL cholesterol levels after administration of statins was significantly smaller in the T carriers compared with the non-T carriers (27.6 vs. 36.4%, P = 0.031). CONCLUSIONS The mutant allele of the C-857T promoter polymorphism of the TNF-alpha gene may predispose to resistance to the LDL cholesterol-lowering effect of statins and could be one of the markers used to predict the efficacy of statins.
目的 有报道称肿瘤坏死因子-α（TNF-α）基因启动子区域的 C-857T 多态性与 LDL 胆固醇水平有关。本研究旨在评估 2 型糖尿病患者中 TNF-α-C-857T 多态性与 LDL 胆固醇水平之间的关系，并根据他汀类药物治疗进行分析。
研究设计与方法 从 322 例日本 2 型糖尿病患者（男性 160 例，女性 162 例）中提取 DNA，并通过直接测序确定 TNF-α-C-857T 多态性。通过直接法测量血清 LDL 胆固醇。
结果 虽然 T 携带者（C/T+T/T）的血清 LDL 胆固醇水平明显高于非 T 携带者（C/C）（3.14±0.86 vs. 2.89±0.75mmol/L，P<0.05），但在未接受他汀类药物治疗的患者中，非 T 携带者和 T 携带者的 LDL 胆固醇水平没有差异（2.87±0.73 vs. 2.89±0.76mmol/L，NS），而在接受他汀类药物治疗的患者中，T 携带者的 LDL 胆固醇水平明显高于非 T 携带者（3.43±0.89 vs. 2.90±0.78mmol/L，P=0.0007）。在他汀类药物治疗和未治疗的患者中，非 T 携带者和 T 携带者的 HDL 胆固醇和甘油三酯水平均无差异。与非 T 携带者相比，T 携带者接受他汀类药物治疗后 LDL 胆固醇水平的降低幅度明显较小（27.6% vs. 36.4%，P=0.031）。
结论 TNF-α 基因启动子区域 C-857T 多态性的突变等位基因可能导致对他汀类药物降低 LDL 胆固醇作用的抵抗，可能是预测他汀类药物疗效的标志物之一。
