Li Ruoyu, Bai Huai, Guan Linbo, Liu Xinghui, Fan Ping, Zhou Mi, Wu Yujie, Wang Yufeng, Zhu Zhengting, Wang Guoyu, Wang Yonghong, Li Dehua
/ ( 610041) West China School of Nursing, Sichuan University/Office of Operations Management and Evaluation, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
( 610041) Laboratory of Genetic Disease and Perinatal Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Jan 20;55(1):125-131. doi: 10.12182/20240160505.
To investigate the -75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene (1) 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.
A total of 626 GDM patients and 1022 normal pregnant women, ie, the controls, were included in the study. The genotyping of 1 -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.
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 1 -75 G/A polymorphism between the GDM and the control group (>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 <0.05). After the GDM patients were divided into obese and non-obese subgroups, the genotype-related 1 variation was observed only in obese patients, while the genotype-related TC and HDL-C variations were evident in non-obese patients (<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 <0.05). Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did (<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.
These results suggest that -75 G/A polymorphism in the 1 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 1 variant-associated lipids and SBP variation is BMI dependent in both groups.
研究载脂蛋白A1基因启动子区域-75G/A单核苷酸多态性及其与孕妇妊娠期糖尿病(GDM)的关系,为探讨GDM的分子遗传基础提供参考。
本研究共纳入626例GDM患者和1022例正常孕妇(即对照组)。采用聚合酶链反应和限制性片段长度多态性(PCR-RFLP)分析对-75G/A多态性进行基因分型。采用酶法测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和葡萄糖(Glu)。采用化学发光免疫分析法测定血浆胰岛素(INS)。采用免疫比浊法测定载脂蛋白A1和载脂蛋白B的蛋白水平。
GDM组G和A等位基因频率分别为0.718和0.282,对照组分别为0.713和0.287。GDM组和对照组的基因型频率分布均符合Hardy-Weinberg平衡。GDM组与对照组之间G和A等位基因频率以及-75G/A多态性基因型频率无显著差异(>0.05)。在GDM组中,基因型为AA的携带者的TC、HDL-C和载脂蛋白A1水平显著高于基因型为GG和GA的携带者(均<0.05)。将GDM患者分为肥胖和非肥胖亚组后,仅在肥胖患者中观察到与基因型相关的1变化,而在非肥胖患者中与基因型相关的TC和HDL-C变化明显(<0.05)。在对照组中,基因型为AA和GA的携带者的收缩压(SBP)和HDL-C高于基因型为GG的携带者(均<0.05)。基因型为AA的携带者的Glu水平显著低于基因型为GG和GA的携带者(<0.05)。根据体重指数(BMI)将对照组进一步分为亚组。亚组分析显示,仅在肥胖对照女性中,AA携带者与较高的SBP水平相关,而在肥胖和非肥胖对照女性中,Glu水平均较低。
这些结果表明,1基因中的-75G/A多态性与GDM无关。然而,这种基因变异与GDM患者的血浆载脂蛋白A1、HDL-C和TC水平以及对照组的血浆HDL-C、Glu和SBP水平密切相关。两组中与1变异相关的脂质和SBP变异均依赖于BMI。