妊娠期糖尿病患者磺脲类药物受体1基因多态性的研究

目的　探讨与妊娠期糖尿病(GDM)遗传易感性相关的磺脲类药物受体 1(SUR1)基因型以及SUR1不同基因型与体重指数 (BMI)、胰岛素分泌水平之间的关系。方法　采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法,检测GDM患者 35例(GDM组)、2型糖尿病的女性住院患者 35例(T2DM组)、正常健康孕妇 35例 (正常对照组 )的SUR1基因型,包括 24内含子 (c和t等位基因,cc、ct和tt基因型)与 31外显子(A和G等位基因,AA、AG和GG基因型);用放射免疫法和葡萄糖氧化酶法测定GDM组患者空腹血糖、空腹胰岛素(INS0 )水平和口服 75g葡萄糖后 2h胰岛素(INS120 )水平。结果　(1)GDM组、T2DM组c等位基因频率 (分别为 70.0%、71.4% )均明显高于正常对照组的(52.9% ), 2组分别与正常对照组比较,差异均有统计学意义 (P<0.05)。(2)GDM组、T2DM组A等位基因频率(分别为 41.4%、44.3% )均明显高于正常对照组的 (24.3% ), 2组分别与正常对照组比较,差异均有统计学意义 (P<0.05 )。 ( 3 )GDM组 24内含子cc基因型患者BMI (29.2±5.6)kg/m2 ]、INS0 (14.9±8.7)mU/L]、INS120 (40.2±12.1)mU/L]均显著高于ct基因型患者BMI(25.2±4.6)kg/m2、INS0 (10.1±6.2)mU/L、INS120 (32.7±10.5)mU/L]及tt基因型患者BMI(24.2±1.7)kg/m2、

Study on association between gestational diabetes mellitus and sulfonylurea receptor-1 gene polymorphism

OBJECTIVE: 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. METHODS: 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)). RESULTS: 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). CONCLUSIONS: 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.