Niu Xiu-min, Yang Hua, Zhang Hui-ying, Li Nai-jun, Qi Xiao-mei, Chang Ying, Chang Zheng, Zhang Ying
Department of Obstetrics and Gynecology, General Hospital of Tianjin Medical University, China.
Zhonghua Fu Chan Ke Za Zhi. 2005 Mar;40(3):159-63.
To investigate allelic frequency of sulfonylurea receptor-1 (SUR1) in gestational diabetes mellitus (GDM) women of Han nationality in north China in order to find out susceptible gene associated with GDM, and to assess the association between SUR1 allele and body mass index (BMI) and secretion of insulin.
Seventy cases of pregnant women were selected. It included 35 cases of pregnant women with GDM (GDM group), 35 cases of normal pregnant women (normal control group). Another 35 women patients with type 2 diabetes in the same period as T2DM group. By using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we detected the distribution of SUR1 alleles frequency in all individuals of three groups. We also examined BMI, fasting insulin (INS(0)) and 2 h insulin levels (INS(120)).
There was significantly increased c alleles frequency of SUR1 in GDM and T2DM women compared with normal pregnancy (70.0%, 71.4% and 52.9%, P < 0.05). Also significantly increased A alleles frequency of SUR1 in GDM and T2DM women was found compared with normal pregnancy (41.4%, 44.3% and 24.3%, P < 0.05). In GDM group, women carrying cc genotype had a higher BMI [(29.2 +/- 5.6) kg/m(2)], INS(0) [(14.9 +/- 8.7) mU/L] and INS(120) [(40.2 +/- 12.1) mU/L] as compared with those in carriers of other genotypes (ct and tt) (all P < 0.05). Also they had a lower insulin sensitivity (HOMA-IR) (3.9 +/- 2.5) as compared with carriers of ct genotype. Women carrying AA genotype had a higher INS(0) as compared with carriers of other genotypes (AG and GG) [(15.4 +/- 3.2), (12.1 +/- 4.5) and (11.5 +/- 4.8) mU/L, both P < 0.05]. Logistic regression analysis showed there was relationship between SUR1 cc genotype and severity of GDM (P = 0.005, RR = 25.128).
There are -3t-->c and A/G polymorphism of SUR1 gene in the Han nationality. Alleles c of SUR1 are significantly implicated in the susceptibility to GDM. It suggests that the defect in SUR1 gene (cc and AA) may contribute to insulin hypersecretion, which might be the cause of increased body weight and decreased insulin sensitivity and genotype cc of SUR1 is connected with severe type of GDM. It might be the predictable index of GDM conversion to type 2 diabetes.
研究中国北方汉族妊娠期糖尿病(GDM)妇女磺脲类受体-1(SUR1)的等位基因频率,以寻找与GDM相关的易感基因,并评估SUR1等位基因与体重指数(BMI)及胰岛素分泌之间的关系。
选取70例孕妇,其中GDM孕妇35例(GDM组),正常孕妇35例(正常对照组),同期2型糖尿病女性患者35例作为T2DM组。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测三组所有个体中SUR1等位基因频率的分布。同时检测BMI、空腹胰岛素(INS(0))和2小时胰岛素水平(INS(120))。
与正常妊娠组相比,GDM组和T2DM组妇女SUR1基因c等位基因频率显著升高(分别为70.0%、71.4%和52.9%,P<0.05)。GDM组和T2DM组妇女SUR1基因A等位基因频率也显著高于正常妊娠组(分别为41.4%、44.3%和24.3%,P<0.05)。在GDM组中,携带cc基因型的妇女BMI[(29.2±5.6)kg/m²]、INS(0)[(14.9±8.7)mU/L]和INS(120)[(40.2±12.1)mU/L]均高于其他基因型(ct和tt)携带者(均P<0.05)。与ct基因型携带者相比,其胰岛素敏感性(HOMA-IR)较低(3.9±2.5)。携带AA基因型的妇女INS(0)高于其他基因型(AG和GG)携带者[(15.4±3.2)、(12.1±4.5)和(11.5±4.8)mU/L,均P<0.05]。Logistic回归分析显示,SUR1基因cc基因型与GDM严重程度有关(P=0.005,RR=25.128)。
汉族人群存在SUR1基因-3t→c和A/G多态性。SUR1基因c等位基因与GDM易感性显著相关。提示SUR1基因缺陷(cc和AA)可能导致胰岛素分泌过多,这可能是体重增加、胰岛素敏感性降低的原因,且SUR1基因cc基因型与重度GDM相关,可能是GDM向2型糖尿病转化的预测指标。