妊娠期糖尿病患者肝脏激酶B1 内含子380C ＞ T 基因多态性与糖脂代谢的关系及评估疾病易感性的价值

目的　探讨妊娠期糖尿病（gestational diabetes mellitus, GDM）患者肝脏激酶B1（liver kinase B1, LKB1）内含子380C ＞ T 基因多态性与糖脂代谢的关系及评估疾病易感性的价值。方法　选取2019 年1 月～ 2021 年4 月成都市双流区第一人民医院收治的92 例GDM 患者作为GDM 组，依据1∶1 对照设计原则，另选同期92 例正常孕妇作为对照组。比较两组一般资料: 糖脂代谢指标[ 空腹血糖（fasting plasma glucose，FPG）、糖化血红蛋白（hemoglobin A1c，HbA1c）]、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）、高密度脂蛋白胆固醇（high densitylipoprotein cholesterol，HDL-C）、三酰甘油（triglyceride，TG）和总胆固醇（total cholesterol，TC）等水平以及LKB1内含子380C ＞ T 基因多态性, 分析糖脂代谢指标水平与基因型的关系及GDM 易感性的相关影响因素。结果　GDM 组有GDM 家族史者占比（18/92, 19.57%）明显高于对照组（3/92, 3.26%），差异有统计学意义（χ2 =12.095，P ＜ 0.01）；GDM组FPG（6.14±0.67 mmol/L ），HbA1c（6.87%±0.31%），LDL-C（3.49±0.25 mmol/L），TG（2.31±0.54 mmol/L），TC（4.88±0.61 mmol/L）水平均明显高于对照组（4.52±0.33 mmol/L，5.09%±0.40%，3.05±0.27mmol/L，1.96±0.48mmol/L，4.39±0.72mmol/L）；HDL-C（1.06±0.19 mmol/L）水平明显低于对照组（1.33±0.22mmol/L），差异均有统计学意义（t=20.805，33.737，11.469，4.647，4.981 和8.909，均P ＜ 0.01）；GDM 组与对照组LKB1 内含子380C ＞ T 基因型中CT（40.22%），TT 基因型（18.48%）占比均明显高于对照组（27.17%，13.04%），CC 基因型（41.30%）明显低于对照组（59.78%），差异有统计学意义（χ2=6.292，P＜ 0.01）；LKB1内含子380C ＞T基因型TT患者HbA1c（7.13%±0.44%）水平高于基因型CT 患者（6.22%±0.39%），基因型CT 患者HbA1c 水平高于基因型CC 患者（5.46%±0.36%），差异有统计学意义（F=228.003，P ＜ 0.01）；且TT 和CT 基因型患者LDL-C 水平（3.59±0.37 mmol/L，3.45±0.32mmol/L）均明显高于CC 型患者LDL-C 水平（3.05±0.29mmol/L），差异有统计学意义（F=48.151，P ＜ 0.01）；HbA1c 与基因型呈强正相关，LDL-C 与基因型呈弱正相关（r=0.815，0.366，均P ＜ 0.01）；有GDM 家族史及LKB1 内含子380C＞ T 基因型TT 均为GDM 易感性的独立危险因素（P ＜ 0.01）。结论　LKB1 内含子380C ＞ T 基因突变可引起机体发生糖脂代谢紊乱，从而增高GDM 易感性，是GDM 发生的危险因素之一。

Relationship between Liver Kinase B1 (LKB1) Intron 380C>T Gene Polymorphism and Glucose and Lipid Metabolism in Patients with Gestational Diabetes Mellitus (GDM) and Evaluate Value in Assessing Disease Susceptibility

Objective　To investigate the relationship between liver kinase B1 (LKB1) intron 380C > T gene polymorphism and glycolipid metabolism in patients with gestational diabetes mellitus (GDM) and assess the susceptibility of disease. Methods　A total of 92 GDM patients admitted to the Chengdu Shuangliu District First People’s Hospital from January 2019 to April 2021 were selected as the GDM group. Based on the 1:1 control design principle, 92 normal pregnant women during the same period were selected as the control group. Compared the general information of the two groups: indicators of glucose metabolism [fasting plasma glucose (FPG), hemoglobin A1c (HbA1c)], low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (high density lipoprotein cholesterol, HDL-C), triglyceride (TG) and total cholesterol (TC), and LKB1 intron 380C>T gene polymorphism. Analysed the relationship of glucose metabolism index levels and genotype, and related influencing factors of GDM susceptibility. Results　The proportion of people with a family history of GDM in the GDM group (18/92, 19.57%) was significantly higher than that in the control group（3/92, 3.26%）, and the difference was statistically significant (χ2=12.095, P ＜ 0.01). The levels of FPG in the GDM group (6.14±0.67 mmol/L), HbA1c (6.87%±0.31%), LDL-C (3.49±0.25 mmol/L), TG (2.31±0.54 mmol/L) and TC (4.88±0.61 mmol/L) were significantly higher than the control group （4.52±0.33 mmol/L，5.09%±0.40%，3.05±0.27mmol/L，1.96±0.48mmol/L，4.39±0.72mmol/L）, and the level of HDL-C (1.06±0.19 mmol/L) was significantly lower than the control group（1.33±0.22mmol/L）,all the differences were statistically significant significance (t=20.805, 33.737, 11.469, 4.647, 4.981 and 8.909, all P ＜ 0.01). GDM group and control group LKB1 intron 380C>T genotype CT (40.22% ) and TT genotype ( 18.48% ) were significantly higher than the control group （27.17%，13.04%）, CC genotype(41.30%) were lower than the control group(59.78%), the difference was statistically significant (χ2=6.292, P ＜ 0.01).In LKB1 intron 380C>T genotype TT patients , the level of HbA1c (7.13%±0.44% ）was higher than that of genotype CT patients（6.22%±0.39 %), and the level of HbA1c in genotype CT patients was higher than that of CC patients（5.46%±0.36%), the difference was statistically significant (F=228.003, P ＜ 0.01). The levels of LDL-C (3.59±0.37 mmol/L and 3.45±0.32 mmol/L) in patients with TT and CT genotypes were significantly higher than that of patients with CC type（3.05±0.29 mmol/L), and the difference was both statistical significance (F=48.151, P ＜ 0.01). HbA1c was strongly positively correlated with genotype, and LDL-C was weakly positively correlated with genotype (r=0.815，0.366, all P ＜ 0.01). GDM with a family history and LKB1 intron 380C>T genotype TT could be independent risk factors for GDM susceptibility (P ＜ 0.01). Conclusion　The mutation of LKB1 intron 380C>T gene can cause disorders of glucose and lipid metabolism in the body, with increasing the susceptibility to GDM.It is one of the risk factors for the occurrence of GDM.