Department of Endocrinology and Metabolism, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Endocrine. 2010 Jun;37(3):507-12. doi: 10.1007/s12020-010-9338-0. Epub 2010 Apr 13.
The purpose of this study is to find out whether the -607 C/A polymorphism in IL-18 gene promoter will affect serum IL-18 concentrations and glucose metabolism in Chinese subjects. In 232 patients with impaired glucose regulation (IGR) or type 2 diabetes and 212 subjects of normal glucose regulation (NGR), -607 C/A polymorphism was analyzed by polymerase chain reaction with sequence specific primers. Serum IL-18 concentrations were determined by ELISA in 200 subjects. Compared with subjects with NGR, those with type 2 diabetes and IGR had significant higher IL-18 concentrations [114.4 (92.9-149.2) and 102.1 (67.5-138.2) vs. 77.3 (53.8-107.8) pg/ml, P = 0.0026 and P < 0.0001, respectively]. A significantly higher proportion of A/A genotype of -607 C/A polymorphism presented in patients with type 2 diabetes compared with subjects of NGR (23.8% vs. 10.9%, P = 0.005). Subjects with an A/A genotype also had higher 2 h post-loading plasma glucose (2 h-PPG) compared with C/A and C/C genotypes even after adjustments of age, sex and BMI [8.94 (7.55-12.3) vs. 7.80 (6.00-9.87) and 7.23 (5.66-8.99) mmol/l, P both < 0.05]. Multiple linear regression revealed that BMI (P < 0.0001) and 2 h-PPG (P = 0.019) were independently associated with IL-18 concentrations. In conclusion, subjects with IGR or type 2 diabetes had significantly higher concentrations of IL-18 than those with NGR. Genotype A/A of IL-18 gene promoter -607 C/A polymorphism was associated with higher prevalence of type 2 diabetes and 2 h post-loading plasma glucose level.
本研究旨在探讨白细胞介素-18（IL-18）基因启动子-607C/A 多态性是否会影响中国人群的血清 IL-18 浓度和糖代谢。在 232 例糖调节受损（IGR）或 2 型糖尿病患者和 212 例血糖正常的受试者中，采用聚合酶链反应-序列特异性引物方法分析-607C/A 多态性。在 200 例受试者中用 ELISA 法测定血清 IL-18 浓度。与血糖正常的受试者相比，2 型糖尿病和 IGR 患者的 IL-18 浓度明显升高[114.4（92.9-149.2）和 102.1（67.5-138.2）与 77.3（53.8-107.8）pg/ml，P=0.0026 和 P<0.0001]。与血糖正常的受试者相比，2 型糖尿病患者-607C/A 多态性 A/A 基因型的比例显著升高（23.8%比 10.9%，P=0.005）。即使在校正年龄、性别和体重指数（BMI）后，A/A 基因型的受试者 2 小时负荷后血浆葡萄糖（2 h-PPG）也高于 C/A 和 C/C 基因型[8.94（7.55-12.3）比 7.80（6.00-9.87）和 7.23（5.66-8.99）mmol/L，P 均<0.05]。多元线性回归显示 BMI（P<0.0001）和 2 h-PPG（P=0.019）与 IL-18 浓度独立相关。结论：IGR 或 2 型糖尿病患者的血清 IL-18 浓度明显高于血糖正常的受试者。IL-18 基因启动子-607C/A 多态性的 A/A 基因型与 2 型糖尿病和 2 h-PPG 水平升高有关。
