Polymorphism Ncol in tumor necrosis factor B is associated with fasting glycemia and lipid parameters in healthy non-obese caucasian subjects.
Polymorphism Ncol in tumor necrosis factor B is associated with fasting glycemia and lipid parameters in healthy non-obese caucasian subjects.
复制标题
肿瘤坏死因子 B 中的 Ncol 多态性与健康非肥胖白种人受试者的空腹血糖和血脂参数相关。
作者：
K. Kankova;I. Márová;E. Jansen;A. Vašků;M. Jurajda;J. Vácha
背景
该研究旨在调查113名接受口服葡萄糖耐量试验（oGTT）的白人受试者中TNF-B Ncol和TNF-α-308 G/A多态性、血浆TNF-α水平以及与胰岛素敏感性相关的代谢和人体测量参数之间的关联。
方法
采用聚合酶链反应（PCR）检测基因型，测定BMI、WHR、oGTT时BMI、空腹免疫反应性胰岛素（IR）、空腹C肽（FSP）、糖化血红蛋白（HbA（1c））、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）及血浆肿瘤坏死因子（TNF-α）水平。
结果
10名受试者被诊断为2型糖尿病，41名受试者被诊断为糖耐量受损（IGT），62名受试者被诊断为正常糖耐量（NGT）。NGT组中TNF-B Ncol基因型间FPG（P=0.0063）、LDL（P=0.0179）和总胆固醇（P=0.0763）差异有统计学意义。根据BMI将NGT患者分为肥胖和非肥胖两组后，仅在非肥胖亚组中证实TNF-B Ncol与FPG、LDL和胆固醇相关。TNF-α-308G/A多态性与研究的任何参数无关。TNF-α水平在NGT、IGT和DM组之间没有差异，也没有基因型依赖性差异。
结论
我们的研究结果表明，在血糖正常的非肥胖白人受试者中，TNF-B Ncol多态性与FPG、LDL和总胆固醇显著相关。该基因多态性可能参与了健康状态下糖脂稳态的遗传调节和胰岛素敏感性的调节。这种调节的紊乱可能是2型糖尿病发病机制的组成部分。
BACKGROUND
The study was designed to investigate the associations among polymorphisms TNF-B Ncol and TNF-alpha -308G/A, plasma TNF-alpha levels and metabolic and anthropometric parameters related to insulin sensitivity in a set of 113 Caucasian subjects undergoing oral glucose tolerance test (oGTT).
METHODS
Genotypes were detected by PCR; BMI, WHR, glycemia during oGTT, fasting immunoreactive insulin, fasting C-peptide, HbA(1c), total cholesterol, triglycerides, HDL, LDL and plasma TNF-alpha levels were measured in each subject.
RESULTS
Type 2 diabetes was diagnosed in 10 subjects, impaired glucose tolerance (IGT) in 41, normal glucose tolerance (NGT) in 62. Significant differences among genotypes of the TNF-B Ncol were observed for FPG (P=0.0063), LDL (P=0.0179) and marginally for total cholesterol (P=0.0763) in NGT group. After the classification of NGT subjects into obese and non-obese according to BMI, associations of TNF-B Ncol with FPG, LDL and cholesterol were proved in non-obese subgroup only. TNF-alpha -308G/A polymorphism was not associated with any of the parameters studied. TNF-alpha levels did not revealed difference among NGT, IGT and DM groups or genotype-dependent differences.
CONCLUSIONS
Our results indicate significant association of the TNF-B Ncol polymorphism with FPG, LDL and total cholesterol in normoglycemic non-obese Caucasian subjects. This polymorphism could be involved in genetic modulation of glucose and lipid homeostasis and regulation of insulin sensitivity already in healthy state. Disturbances of this regulation could be component of pathogenesis of type 2 diabetes mellitus.