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

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。

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

OBJECTIVE: To study allelic frequency of tumor necrosis factor-alpha (TNF-alpha) in gestational diabetes mellitus (GDM) of Han ethnicity in north China and to determine whether there is a specific allele of TNF-alpha associated with GDM susceptibility. METHODS: By using PCR-RFLP, we detected the distribution of TNF-alpha promoter alleles frequency in GDM women and control normal pregnant women. Plasma TNF-alpha levels and insulin levels were measured by radioimmunoassay. RESULTS: (1) There was a significant increase of A alleles frequency of TNF-alpha 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-alpha 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-alpha promoter gene is involved in the pathophysiology of insulin resistance and gestational diabetes mellitus.