探讨葡萄糖激酶调节蛋白(GCKR)基因rs780094(C>T)多态性与妊娠期糖尿病(GDM)发病风险的相关性。

选择2013年2月至2016年7月，于西北妇女儿童医院妇产科就诊的252例孕妇为研究对象。其中127例为GDM孕妇，纳入GDM组；125例为健康孕妇，纳入对照组。收集2组孕妇的相关临床资料及实验室检测结果。GCKR基因rs780094(C>T)多态性基因型频率，采用实时荧光定量PCR法进行检测。采用成组t检验，对2组孕妇人体质量指数(BMI)，总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、尿素浓度，以及总蛋白、白蛋白水平进行比较。采用Mann-Whitney U检验，对2组孕妇空腹血糖、75 g口服葡萄糖耐量试验(OGTT) 2 h血糖、三酰甘油、肌酐、尿酸浓度进行比较。采用χ²检验，对2组孕妇的妊娠期高血压疾病发生率、有糖尿病家族史所占比例，以及GCKR基因rs780094(C>T)多态性基因型、等位基因频率进行比较。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》的要求，并与所有孕妇签署临床研究知情同意书。2组孕妇年龄等一般临床资料比较，差异均无统计学意义(P>0.05)。

①与对照组孕妇相比较，GDM组孕妇BMI、妊娠期高血压疾病发生率、有糖尿病家族史所占比例及空腹血糖、75 g OGTT 2 h血糖、三酰甘油、尿酸浓度均显著升高，而总蛋白、白蛋白水平及肌酐、尿素浓度均显著降低，并且差异均有统计学意义(t＝－8.087，χ²＝7.280、135.428，Z＝－2.752、－3.764、－4.657、－2.631，t＝5.957、11.810，Z＝2.389，t＝6.528；P<0.05)。②GDM组和对照组孕妇GCKR基因rs780094(C>T)多态性基因型频率分布，均符合Hardy-Weinberg平衡定律(χ²＝0.758、P＝0.685, χ²＝1.440、P＝0.487)。在共显性模型下，GDM组孕妇GCKR基因rs780094(C>T)多态性CC、CT、TT基因型频率分别为50.4%(64/127)、37.8%(48/127)、11.8%(15/127)，对照组分别为34.4%(43/125)、54.4%(68/125)、11.2%(14/125)，2组比较，差异有统计学意义(χ²＝7.589、P＝0.022)；在显性模型下，GDM组孕妇CC、CT＋TT基因型频率分别为50.4%(64/127)、49.6%(63/127)，对照组分别为65.6%(82/125)、11.2%(14/125)，2组比较，差异亦有统计学意义(χ²＝6.956、P＝0.010)。对照组T等位基因频率为38.4%(96/250)。

携带GCKR基因rs780094(C>T)多态性C等位基因的孕妇发生GDM的风险升高。因本研究纳入样本量相对较小，GCKR基因rs780094(C>T)多态性与GDM发病风险的相关性，尚需更多大样本、前瞻性随机对照研究结果证实。

To explore the correlation between GCKR gene rs780094 (C>T) polymorphism and the onset risk of gestational diabetes mellitus (GDM).

A total of 252 cases of pregnant women who were treated in Northwest Women and Children′s Hospital were selected as research subjects. They were divided into GDM group which included 127 cases of GDM pregnant women, and control group which included 125 cases of healthy pregnant women. The clinical and laboratory data of each group were collected. The genotypes of GCKR gene rs780094 (C>T) polymorphism were detected by PCR with fluorescent probes. Independent-samples t test was used to compare the body mass index (BMI), and concentrations of 1, 5-anhydro-D-glucitol (AG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and urea, and levels of total protein and albumin between two groups. Mann-Whitney U test was used to compare the concentrations of fasting blood glucose, 75 g oral glucose tolerance test (OGTT) 2 h blood glucose, trigalloyl glycerol, creatinine and uric acid between two groups. Chi-square test was used to compared the incidence of hypertensive disorder complicating pregnancy, the proportion of family history of diabetes, and genotype and allele frequencies of GCKR gene rs780094 (C>T) polymorphism between two groups. The study met the requirements of World Medical Association Declaration of Helsinki revised in 2013 and informed consents for clinical research were signed by all the pregnant women. There were no statistical differences between two groups in the aspects of age and other general clinical data (P>0.05).

①Compared with pregnant women in control group, the BMI, incidence of hypertensive disorder complicating pregnancy, the proportion of family history of diabetes, and concentrations of fasting blood glucose, 75 g OGTT 2 h blood glucose, trigalloyl glycerol and uric acid were significantly increased in the GDM group, while levels of total protein and albumin, and concentrations of creatinine and urea were significantly decreased, and all the differences were statistically significant (t=-8.087, χ²=7.280, 135.428; Z=-2.752, -3.764, -4.657, -2.631; t=5.957, 11.810; Z=2.389, t=6.528; all P<0.05). ②The genotypes distributions of GCKR gene rs780094 (C>T) polymorphism of GDM group and control group both were in line with the Hardy-Weinberg equilibrium law (χ²=0.758, P=0.685; χ²=1.440, P=0.487). In codominant model of GCKR gene rs780094 (C>T) polymorphism, genotype frequencies of CC, CT and TT were 50.4% (64/127), 37.8% (48/127), and 11.8% (15/127), respectively in GDM group, and 34.4% (43/125), 54.4% (68/125), and 11.2% (14/125), respectively in control group, and there was statistically significant difference between two group in genotype frequencies of CC, CT and TT (χ²=7.589, P=0.022). In dominant model of GCKR gene rs780094 (C>T) polymorphism, genotype frequencies of CC and CT/TT were 50.4% (64/127) and 49.6% (63/127), respectively in GDM group, and 65.6% (82/125), 11.2% (14/125), respectively in control group, and there was statistically significant difference between two group in genotype frequencies of CC and CT/TT (χ²=6.956, P=0.010). The minor T allele frequency in the control group was 38.4% (96/250).

Pregnant women carriers of C allele GCKR gene rs780094 (C>T) polymorphism are more likely to develop into GDM. Because of the relatively small sample size in this study, the association between the GCKR gene rs780094 (C>T) polymorphism and the risk of GDM needs more large-sample prospective randomized controlled trials to confirm.