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正常孕妇及妊娠糖尿病患者apoA1基因启动子区－75 G/A多态性的研究
－75 G/A Polymorphism of Apolipoprotein A1 Gene Promoter Region in Normal Pregnant Women and Patients With Gestational Diabetes Mellitus
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摘要:目的 研究载脂蛋白A1（apoA1）基因启动子区－75 G/A (apoA1 －75 G/A)单核苷酸多态性是否与妊娠糖尿病（GDM）有关联，为探讨本病的分子遗传基础提供依据。方法 应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测1022名正常妊娠对照者和626例GDM患者apoA1 －75 G/A基因多态性。酶法测定总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）和血糖（Glu），化学发光法测定血浆胰岛素（INS）。免疫透射比浊法测定载脂蛋白A1（apoA1）和B（apoB）水平。结果 apoA1 －75 G/A多态位点等位基因G、A频率在GDM组和对照组分别为0.718、0.282和0.713、0.287。两组人群基因型频率分布均符合Hardy-Weinberg平衡定律。apoA1 －75 G/A多态性基因型频率、等位基因G、A频率在GDM组和正常对照组间比较差异无统计学意义（P>0.05）。在GDM组apoA1 －75 G/A多态性AA基因型者较GG型者、GA型者在TC、HDL-C和apoA1水平均增高（P均<0.05）；GDM患者进一步划分为肥胖和非肥胖亚组后，apoA1基因型与apoA1水平的关系仅在肥胖亚组观察到，与TC和HDL-C的关系在非肥胖亚组观察到（P<0.05）。与GG基因型者比较，正常妊娠对照组AA和GA基因型者的收缩压（SBP）和HDL-C水平均有所升高（P均<0.05）；AA基因型者较GG型和GA型者Glu水平降低（P<0.05）。对照组人群按体质量指数（BMI）分亚组后基因型与SBP和HDL-C水平的关系仅在肥胖对照亚组观察到，与Glu水平的关系在肥胖和非肥胖亚组均存在。结论 apoA1 －75 G/A多态性与GDM无关联，但该变异与GDM患者血浆apoA1、HDL-C和TC水平密切有关。该基因位点的变异在正常妊娠孕妇中与血浆HDL-C、Glu和SBP水平相关联。该变异在两组人群与血脂和血压水平改变的关系具有BMI依赖的特性。Abstract:Objective To investigate the －75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene (apoA1) and its association with gestational diabetes mellitus (GDM) in pregnant women and to provide references for the exploration in the molecular genetic basis of GDM.Methods A total of 626 GDM patients and 1022 normal pregnant women, ie, the controls, were included in the study. The genotyping of apoA1 －75 G/A polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence immunoassay. The protein levels of apoA1 and apoB were measured by the turbidimetric immunoassay.Results Allele frequencies of G and A were 0.718 and 0.282 in the GDM group and 0.713 and 0.287 in the control group, respectively. Distribution of the genotype frequencies was found to be in Hardy-Weinberg equilibrium in both the GDM and control groups. There was no significant difference in the frequencies of alleles G and A and the genotypes of apoA1 －75 G/A polymorphism between the GDM and the control group (P>0.05). In the GDM group, the carriers with the genotype AA were associated with significantly higher levels of TC, HDL-C, and apoA1 than those with genotypes GG and GA did (all P<0.05). After the GDM patients were divided into obese and non-obese subgroups, the genotype-related apoA1 variation was observed only in obese patients, while the genotype-related TC and HDL-C variations were evident in non-obese patients (P<0.05). In the control group, carriers of genotypes AA and GA had higher systolic blood pressure (SBP) and HDL-C than the carriers of genotype GG did (all P<0.05). Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did (P<0.05). The control subjects were further divided into subgroups according to their body mass index (BMI). Analysis of the subgroups showed that AA carriers were associated with higher SBP levels in the obese control women only, while lower Glu levels were evident in both obese and non-obese control women.Conclusion These results suggest that －75 G/A polymorphism in the apoA1 gene is not associated with GDM. However, the genetic variation is closed associated with the plasma apoA1, HDL-C, and TC levels in GDM patients and plasma HDL-C, Glu, and SBP levels in the control subjects. The apoA1 variant-associated lipids and SBP variation is BMI dependent in both groups.
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