Wang C-P, Hung W-C, Yu T-H, Chiu C-A, Lu L-F, Chung F-M, Hung C-H, Shin S-J, Chen H-J, Lee Y-J
Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Exp Clin Endocrinol Diabetes. 2010 Jun;118(6):346-52. doi: 10.1055/s-0029-1243604. Epub 2010 Feb 5.
Cytochrome P450 (CYP) 2J2 is a regulatory enzyme in the biosynthesis of biologically active CIS-epoxyeicosatrienoic acids (EETs). EETs have been suggested to modulate PPAR-gamma and PPAR-alpha transcription activity and play a role in stimulus-secretion coupling in pancreatic beta cells. Genetic abnormalities in the expression of CYP2J enzymes may play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our objective was to investigate CYP2J2 G-50T polymorphism (rs890293) in association with insulin resistance markers and T2DM in a Chinese population.
A total of 1 747 Chinese T2DM patients and 994 non-diabetic subjects were studied. The CYP2J2 G-50T polymorphism was determined by a restriction fragment-length polymorphism polymerase chain reaction.
Neither the CYP2J2 genotype distribution nor allele frequency differed between the control subjects and the T2DM patients. However, among diabetics, subjects with a younger age at diagnosis (AAD; <40 years) had significantly higher T variant frequency than those with an AAD>/=40 years. When diabetic patients were stratified by their AAD in 10-year intervals, the trend was significantly linear among age grades. A significant interaction between the CYP2J2 T variant and younger onset diabetic subjects with positive family diabetes history, and BMI>/=27 kg/m (2) were observed to have the highest risk of diabetes and younger onset diabetics with the T variant had higher homeostasis model assessment estimate of insulin resistance (HOMA-IR) and HOMA-beta values than their GG genotype counterparts. Plasma concentrations of stable EET metabolites were significantly lower in individuals with the G-50T SNP in younger onset diabetics.
These data suggest that age of onset, family history, and obesity may modify the association between the CYP2J2 G-50T polymorphism and T2DM risk. CYP2J2 G-50T polymorphism may contribute to the pathogenesis of T2DM, partially by effects on insulin resistance, in patients with younger onset T2DM.
细胞色素P450（CYP）2J2是生物活性顺式环氧二十碳三烯酸（EETs）生物合成中的一种调节酶。有研究表明，EETs可调节过氧化物酶体增殖物激活受体γ（PPAR-γ）和过氧化物酶体增殖物激活受体α（PPAR-α）的转录活性，并在胰腺β细胞的刺激-分泌偶联中发挥作用。CYP2J酶表达的基因异常可能在2型糖尿病（T2DM）的发病机制中起作用。我们的目的是在中国人群中研究CYP2J2 G-50T多态性（rs890293）与胰岛素抵抗标志物及T2DM的关系。
共研究了1747例中国T2DM患者和994例非糖尿病受试者。采用限制性片段长度多态性聚合酶链反应测定CYP2J2 G-50T多态性。
对照组和T2DM患者之间的CYP2J2基因型分布和等位基因频率均无差异。然而，在糖尿病患者中，诊断时年龄较小（AAD；<40岁）的受试者T变异频率显著高于AAD≥40岁的受试者。当糖尿病患者按10年间隔的AAD分层时，年龄组之间的趋势呈显著线性。观察到CYP2J2 T变异与糖尿病家族史阳性且发病年龄较小的受试者之间存在显著交互作用，体重指数（BMI）≥27 kg/m²的发病年龄较小的糖尿病患者患糖尿病风险最高，且携带T变异的发病年龄较小的糖尿病患者的胰岛素抵抗稳态模型评估值（HOMA-IR）和HOMA-β值高于其GG基因型对应者。发病年龄较小的糖尿病患者中携带G-50T单核苷酸多态性（SNP）个体的血浆稳定EET代谢产物浓度显著降低。
这些数据表明，发病年龄、家族史和肥胖可能会改变CYP2J2 G-50T多态性与T2DM风险之间的关联。CYP2J2 G-50T多态性可能部分通过影响胰岛素抵抗，在发病年龄较小的T2DM患者的发病机制中起作用。
