肿瘤坏死因子α启动子基因多态性与妊娠期糖尿病的相关性研究

Study on the association between gestational diabetes mellitus and tumor necrosis factor-alpha gene polymorphism

目的探讨肿瘤坏死因子α(TNF-α)启动子基因多态性及其血浆水平与妊娠期糖尿病(GDM)发病的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测35例GDM孕妇(GDM组)及35例正常孕妇(对照组)TNF-α启动子-308基因型。采用放射免疫法测定两组孕妇血浆中TNF-α水平及计算胰岛素抵抗指数。结果(1)GDM组A等位基因频率(61·4%)显著高于对照组(30·0%),GA+AA型基因频率(71·4%)也显著高于对照组(37·1%),两组比较,差异有统计学意义(P<0·01)。(2)GDM组孕妇血浆TNF-α水平为(52±13)fmol/L,对照组为(14±4)fmol/L,两组比较,差异有统计学意义(P<0·05)。(3)GDM组胰岛素抵抗指数为13·6±6·5,对照组为1·9±0·2,两组比较,差异有统计学意义(P<0·05)。结论TNF-α-308G/A基因多态性与GDM发病有关,其机制可能是通过升高GDM孕妇血浆TNF-α水平,产生胰岛素抵抗而导致GDM的发生。

Objective To study allelic frequency of tumor necrosis factor-α（TNF-α） in gestational diabetes mellitus （ GDM ） of Han ethnicity in north China and to determine whether there is a specific allele of TNF-α associated with GDM susceptibility. Methods By using PCR-RFLP, we detected the distribution of TNF-α promoter alleles frequency in GDM women and control normal pregnant women. Plasma TNF-α levels and insulin levels were measured by radioimmunoassay. Results （ 1 ） There was a significant increase of A alleles frequency of TNF-α promoter -308 gene in GDM women compared with control group（61.4% vs 30.0% , P 〈 0.05） and an increase of the AA ＋ GA genotype was observed in GDM group （71.4% vs 37. 1% ,P 〈 0.05）. （2）In GDM group, the patients carrying the AA ＋ GA genotype had higher plasma TNF-α levels （52 ± 13 vs 14 ±4,P 〈0. 05） and a lower insulin sensitivity （ 13.6 ±6. 5 vs 1.9 ±0. 2 ,P 〈 0. 05） compared with those carrying the other genotype （GG）. Conclusions The 308 G→A polymorphism of TNF-α promoter gene is involved in the pathophysiology of insulin resistance and gestational diabetes mellitus.