Ukkola O, Salonen J, Kesäniemi Y Antero
Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.
J Endocrinol Invest. 2005 Nov;28(10):871-5. doi: 10.1007/BF03345317.
To identify genetic factors related to individual differences in lipid responses to intensified treatment in Type 2 diabetes.
After evaluation and intensification of their treatment, 107 Type 2 diabetes patients with poor metabolic control were re-evaluated after mean follow-up time of 15.6 (0, 4) (SE) months. The genes coding major lipid regulatory proteins and their relations to plasma lipid and lipoprotein changes were studied.
During the follow-up, levels of glycohemoglobin A1 (GHBA1) decreased (-1.7%), plasma HDL cholesterol (+0.05 mmol/l) and lipoprotein (a) [Lp(a)] (+4.2 mg/dl) increased, while triglyceride (TG) levels decreased (-1.2mmol/l) despite mean weight gain of 2.1 kg (p from <0.01 to <0.001). Of the gene markers studied, the lipoprotein lipase (LPL) Pvull (p=0.005) independently affected changes in HDL-cholesterol and was associated with the frequency of coronary heart disease (CHD). Lp(a) changes were associated with apolipoprotein B (ApoB) Glu4154Lys polymorphism (p=0.004).
These results suggest that genetic variations at LPL and ApoB loci are among the factors contributing to the variability in response to lipid parameters to therapy in Type 2 diabetes. LPL Pvull rare allele homozygote status seems to be beneficial with more favorable lipid changes and protection against CHD.
确定与2型糖尿病强化治疗中血脂反应个体差异相关的遗传因素。
对107例代谢控制不佳的2型糖尿病患者进行评估并强化治疗，平均随访15.6（0，4）（标准误）个月后再次评估。研究编码主要脂质调节蛋白的基因及其与血浆脂质和脂蛋白变化的关系。
随访期间，糖化血红蛋白A1（GHBA1）水平下降（-1.7%），血浆高密度脂蛋白胆固醇（+0.05 mmol/l）和脂蛋白（a）[Lp（a）]（+4.2 mg/dl）升高，而甘油三酯（TG）水平下降（-1.2 mmol/l），尽管平均体重增加了2.1 kg（P值从<0.01至<0.001）。在所研究的基因标记中，脂蛋白脂肪酶（LPL）PvuII（P = 0.005）独立影响高密度脂蛋白胆固醇的变化，并与冠心病（CHD）的发生频率相关。Lp（a）的变化与载脂蛋白B（ApoB）Glu4154Lys多态性相关（P = 0.004）。
这些结果表明，LPL和ApoB基因座的遗传变异是导致2型糖尿病患者对脂质参数治疗反应变异性的因素之一。LPL PvuII罕见等位基因纯合子状态似乎有益，可带来更有利的脂质变化并预防冠心病。
