摘要【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 Hind Ⅲ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 Hind Ⅲ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 Hind Ⅲ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 Hind Ⅲ位点基因多态性与GDM患者及子代IR相关,TNF-α CT基因型和LPL HindⅢ H+ H+基因型患者更易发生IR,促进GDM的发生、发展。
Abstract:【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-α gene -857C/T site, -863A/C site and LPL HindⅢ genotype in pregnant women. The distribution of TNF-αgene -857C/T, -863A/C and LPL HindⅢ were compared between the two groups.The levels of homeostasis model assessment of insulin resistance (HOMA-IR) serum TNF-α and 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 HindⅢ genotype 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 HindⅢ was 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-α and 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-α gene -857C/T site and LPL Hind Ⅲ gene polymorphisms are related to IR in GDM patients and their newborns. The IR is more likely to occur in patients with TNF-α CT genotype and LPL Hind Ⅲ H+ H+ genotype, which leaded to the occurrence and development of GDM.
张俊, 张立文, 李和平. 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[J]. 医学临床研究, 2022, 39(10): 1524-1527.
ZHANG Jun, ZHANG Li-wen, LI He-ping. Relationship between TNF-α and LPL Gene Polymorphisms and Insulin Resistance in GDM Patients and Their Newborns. JOURNAL OF CLINICAL RESEARCH, 2022, 39(10): 1524-1527.
[1] 呼延芳,赵静. 血清糖化白蛋白水平对妊娠期糖尿病孕妇妊娠结局的影响[J].医学临床研究,2022,39(3):475-477.
[2] MOHAMED H E,ASKER M E,KESHAWY M M,et al.Inhibition of tumor necrosis factor-α enhanced the antifibrotic effect of empagliflozin in an animal model with renal insulin resistance[J].Mol Cell Biochem,2020,466(1):45-54.
[3] 罗丽娅,魏在荣,阳琰,等.2型糖尿病合并下肢动脉粥样硬化病变患者血清脂蛋白相关磷脂酶A2、25羟维生素D与同型半胱氨酸关系的研究[J].中国糖尿病杂志,2020,28(1):44-48.
[4] HOD M,KAPUR A,SACKS D A,et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on gestational diabetes mellitus:A pragmatic guide for diagnosis,management,and care[J].Int J Gynaecol Obstet,2015,131(3):173-211.
[5] 李红妮,郭亮,席翠萍. 血清MMP-9、β-hCG联合检测对胎膜早破合并宫内支原体感染的预测价值[J].医学临床研究,2022,39(6):843-846.
[6] HULMAN A,WAGNER,RÓBERT,VISTISEN D,et al. Glucose measurements at various time points during the OGTT and their role in capturing glucose response patterns[J].Diabetes Care,2019,42(4):e56-e59.
[7] 胡晓英,邢忠莹,曹婷婷,等. 吡格列酮联合二甲双胍治疗激素抵抗性PCOS不孕对患者性激素、炎症因子水平的影响[J].医学临床研究,2022,39(5):678-681.
[8] 王成美,曾红兵.高强度运动诱发肌肉损伤对血糖调节、肌酸激酶、IL-6、TNF-α水平的影响[J].基因组学与应用生物学,2018,37(3):970-975.
[9] 陈书英,王光慧,赵馨,等.TNF-α基因多态性与妊娠期糖尿病相关性研究[J].徐州医学院学报,2016,36(10):648-651.
[10] 布帕提玛穆?阿布都克热穆,伊力哈木?乃扎木,宋曼殳,等.维吾尔族群体脂蛋白脂酶基因HindⅢ多态性与血生化指标的相关性[J].解剖学杂志,2016,39(2):218-221.
[11] 郭晓霞,梅颉,侯艳,等.脂蛋白脂酶基因多态性对子痫前期患病风险及血清脂质影响的研究[J].检验医学与临床,2019,16(5):81-86.
[12] 李丹丹,刘扬,苏冬月,等.妊娠期糖尿病患者胎盘组织脂蛋白酶基因多态性与患者胰岛素抵抗的关系探讨[J].现代预防医学,2018,45(12):2154-2157.