Jang Yangsoo, Kim Hyae Jin, Koh Soo Jeong, Hyun Yae Jung, Chae Jey Sook, Cho Hongkeun, Ha Jong-Won, Kim Byung-Keuk, Kim Jung-Sun, Lee Jong Ho
Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei Univ., Seoul, Republic of Korea.
Clin Chim Acta. 2007 Sep;384(1-2):124-8. doi: 10.1016/j.cca.2007.06.017. Epub 2007 Jul 4.
Associations between variations in the lymphotoxin-alpha (LTA) gene and coronary artery disease (CAD) and type 2 diabetes have previously been reported. We investigated the influence of the LTA 252A>G and 804C>A polymorphisms on circulating parameters related to metabolic syndrome in Korean patients with CAD.
The study subjects comprised 446 Korean male patients with CAD (age 53.9 y, BMI 25.2 kg/m2).
The LTA 252A>G and 804C>A polymorphisms were almost in complete linkage disequilibrium (R(2)=99.4%). The LTA 252A>G polymorphism was associated with LDL particle size (P=0.046), HOMA-IR (P=0.022) and circulating levels of triglyceride (P=0.006), HDL-cholesterol (P=0.008), apo A1 (P=0.031), insulin (P=0.046), and adiponectin (P=0.018), after adjustment for BMI. CAD patients with LTA 252G/G (n=96) had a lower concentration of HDL-cholesterol, a smaller LDL particle size, and a higher triglyceride level, compared to those with 252A/A (n=121) or 252A/G (n=229). In addition, CAD patients with LTA 252G/G had lower concentrations of adiponectin and higher levels of insulin, and HOMA-IR than those with 252A/A.
Homozygosity for rare alleles of the LTA 252A>G polymorphisms was associated with features of metabolic syndrome such as hyperinsulinemia, dyslipidemia, small LDL particle and low adiponectin level in CAD patients, suggesting that CAD patients with LTA 252GG are at high risk and needed an intensive intervention against further progression.
先前已有报道淋巴毒素-α(LTA)基因变异与冠状动脉疾病(CAD)及2型糖尿病之间的关联。我们研究了LTA 252A>G和804C>A多态性对韩国CAD患者中与代谢综合征相关的循环参数的影响。
研究对象包括446名韩国男性CAD患者(年龄53.9岁,体重指数25.2kg/m²)。
LTA 252A>G和804C>A多态性几乎完全连锁不平衡(R²=99.4%)。校正体重指数后,LTA 252A>G多态性与低密度脂蛋白颗粒大小(P=0.046)、稳态模型评估胰岛素抵抗(HOMA-IR)(P=0.022)以及甘油三酯循环水平(P=0.006)、高密度脂蛋白胆固醇(P=0.008)、载脂蛋白A1(P=0.031)、胰岛素(P=0.046)和脂联素(P=0.018)相关。与携带252A/A(n=121)或252A/G(n=229)的CAD患者相比,携带LTA 252G/G(n=96)的CAD患者高密度脂蛋白胆固醇浓度较低、低密度脂蛋白颗粒较小且甘油三酯水平较高。此外,携带LTA 252G/G的CAD患者脂联素浓度较低、胰岛素水平较高且HOMA-IR高于携带252A/A的患者。
LTA 252A>G多态性罕见等位基因的纯合性与CAD患者的代谢综合征特征相关,如高胰岛素血症、血脂异常、小低密度脂蛋白颗粒和低脂联素水平,提示携带LTA 252GG的CAD患者风险较高,需要针对进一步进展进行强化干预。