TNF-α和LPL基因多态性与GDM患者及新生儿胰岛素抵抗的关系

Relationship between TNF-αand LPL Gene Polymorphisms and Insulin Resistance in GDM Patients and Their Newborns

【目的】探讨肿瘤坏死因子-α(TNF-α)和脂蛋白酶(LPL)基因多态性与妊娠糖尿病(GDM)患者及新生儿胰岛素抵抗(IR)的关系。【方法】选取2018年10月至2019年10月在西安交通大学第一附属医院诊治的54例GDM患者(观察组),另外收集西安交通大学第一附属医院定期产检的54例正常孕妇(对照组)。采用聚合酶联反应-限制性片段长度多态性(PCR-RFLP)检测所有孕妇TNF-α基因-857C/T位点、-863A/C位点及LPL HindⅢ基因型分布并比较;记录不同基因型GDM患者新生儿胰岛素抵抗指数(HOMA-IR)、血清TNF-α及LPL水平;分析孕妇血清TNF-α和LPL与HOMA-IR的关系。【结果】观察组和对照组孕妇-857C/T位点基因型和等位基因分布比较,差异有统计学意义(P<0.05);观察组CT基因型和T等位基因患者显著高于对照组,差异有统计学意义(P<0.05);观察组和对照组孕妇-863A/C位点基因型和等位基因分布比较,差异无统计学意义(P<0.05)。两组孕妇LPL HindⅢ位点基因型与等位基因分布比较,差异有统计学意义(P<0.05)。观察组H^(+)H^(+)基因型和H^(+)等位基因患者显著高于对照组,差异有统计学意义(P<0.05)。GDM患者-857C/T位点CT基因型患者血清TNF-α、HOMA-IR及新生儿HOMA-IR显著高于CC基因型和TT基因型患者,LPL HindⅢ位点H^(+)H^(+)基因型患者血清LPL显著低于H^(-)H^(-)和H^(+)H^(-)基因型患者,孕妇HOMA-IR及新生儿HOMA-IR显著高于H^(-)H^(-)和H^(+)H^(-)基因型者,差异均有统计学意义(P<0.05)。孕妇血清TNF-α与孕妇和新生儿HOMA-IR水平呈显著正相关(P<0.05),LPL与孕妇和新生儿HOMA-IR水平呈显著负相关(P<0.05)。【结论】TNF-α基因-857C/T位点和LPL HindⅢ位点基因多态性与GDM患者及子代IR相关,TNF-αCT基因型和LPL HindⅢH^(+)H^(+)基因型患者更易发生IR,促进GDM的发生、发展。

【Objective】To study the relationship between tumor necrosis factor-α(TNF-α)and lipoprotein lipase(LPL)gene polymorphisms and insulin resistance(IR)in gestational diabetes mellitus(GDM)patients and their newbornsnewborns.【Methods】54 patients with GDM from October 2018 to October 2019 were included as the observation group,another 54 normal pregnant women were included as the control group.The venous blood of pregnant women were collected,the polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP)were used to detect the distribution of TNF-αgene-857C/T site,-863A/C site and LPL HindⅢgenotype in pregnant women.The distribution of TNF-αgene-857C/T,-863A/C and LPL HindⅢwere compared between the two groups.The levels of homeostasis model assessment of insulin resistance(HOMA-IR)serum TNF-αand LPL were recorded.The relationship between serum TNF-α,LPL and HOMA-IR in pregnant women were analyzed.【Results】There were significant differences in genotype and allele distribution of-857C/T locus between the observation group and the control group(P<0.05).The patients with CT genotype and T allele in the observation group were significantly higher than those in the control group,the difference were statistically significant(P<0.05).There were significant difference in the distribution of LPL HindⅢgenotype and allele between the two groups(P<0.05),the patients with H^(+)H^(+)genotype and H^(+)allele in the observation group were significantly higher than those in the control group,the difference were statistically significant(P<0.05).The levels of serum TNF-α,HOMA-IR and newborn HOMA-IR in patients with GDM of CT genotype at-857C/T were significantly higher than those in patients with CC and TT,the serum LPL of patients with H^(+)H^(+)genotype of LPL HindⅢwas significantly lower than that of patients with H^(-)H^(-)and H^(+)genotype,the HOMA-IR and newborn HOMA-IR were significantly higher than H^(-)H^(-)and H^(+)genotypes,the difference were statistically significant(P<0.05).There were significant positive correlation between serum TNF-αand HOMA-IR of pregnant women and newborns(P<0.05),There were significant negative correlation between LPL and HOMA-IR in pregnant women and newborns(P<0.05).【Conclusion】The TNF-αgene-857C/T site and LPL HindⅢgene polymorphisms are related to IR in GDM patients and their newborns.The IR is more likely to occur in patients with TNF-αCT genotype and LPL HindⅢH^(+)H^(+)genotype,which leaded to the occurrence and development of GDM.