内皮型一氧化氮合酶基因G894T位点多态性与妊娠期高血压疾病患者脂代谢的相关性

李靖云; 刘慧丽

doi:10.16098/j.issn.0529-1356.2022.06.007

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解剖学报 ›› 2022, Vol. 53 ›› Issue (6) : 737-743. DOI: 10.16098/j.issn.0529-1356.2022.06.007

内皮型一氧化氮合酶基因G894T位点多态性与妊娠期高血压疾病患者脂代谢的相关性

李靖云路运华郑莉霞赵岗刘慧丽*

作者信息 +

Relationship between the G894T polymorphism of endothelial nitric oxide synthase gene and lipid metabolism among hypertensive disorder complicating pregnancy patients

LI Jing-yun LU Yun-hua ZHENG Li-xia ZHAO Gang LIU Hui-li*

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文章历史 +

摘要

目的探讨内皮型一氧化氮合成酶（eNOS）基因G894T位点多态性与妊娠期高血压疾病（HDCP）患者脂代谢的相关性。方法选择邢台市第三医院2016年1月~2020年1月收治的528例HDCP患者为研究对象，并以同期128例正常妊娠者作为对照组。采集所有研究对象清晨空腹外周静脉血，并检测血脂指标、胱抑素 (CysC) 及尿酸等生化指标水平。根据血脂水平分为血脂正常组和异常组，血脂异常组包括4个亚组［高三酰甘油(TG)血症组(TG≥1.70mmol/L)、低高密度脂蛋白胆固醇(HDL-C)血症组(HDL-C<1.04mmol/L)、高总胆固醇(TC)血症组(TC≥5.18mmol/L)、混合型高脂血症组(TG≥1.70mmol/L、TC≥5.18mmol/L)］。另采用聚合酶链反应-限制性内切酶长度片段多态性(PCR-RFLP)方法对eNOS基因G894T位点进行基因分型分析，分为TT、GT、GG基因型。比较不同血脂水平者的基因多态性分布情况，并采用Logistic 回归分析方法探讨血脂异常影响因素以及eNOS基因G894T位点多态性与血脂异常之间的关系。结果研究组和对照组中GG、GT、TT eNOS基因G894T位点基因型的期望值和观测值均符合Hardy-Weinberg平衡定律（χ2=0.651，P=0.722； χ2=1.845，P=0.98)且研究组GG型基因频率和G等位基因频率高于对照组，TT型基因频率和T等位基因频率低于对照组(P<0.5)；血脂异常组患者身体质量指数（BMI）、尿微量白蛋白与肌酐比值(UACR)、同型半胱氨酸(Hcy)、尿酸以及C-应蛋白（CRP）水平相较于血脂正常组显著升高，但其降压药服用率更低(P<0.5)。血脂异常组 eNOS基因（G894T）基因的GG基因频率和G等位基因高于血脂正常组，TT基因频率和T等位基因低于血脂正常组(P<0.01)。低HDL-血症组、高TG血症组以及混合型高脂血症组患者的BMI均高于血脂正常组(P<0.5)；混合型高脂血症组患者Hcy水平高于血脂正常组(P<0.5)。低HDL-血症组和混合型高脂血症组的TT基因频率和T等位基因明显低于血脂正常组，GG基因频率和和G等位基因频率高于血脂正常组(P<0.5)。Logistic回归分析表明，基因型TT属于HDCP血脂水平异常的一种保护因素，基因型GG、高BMI、高Hcy水平属于血脂异常的独立危险因素。结论妊娠期高血压疾病患者的eNOS基因G894T位点多态性与血脂异常之间相关性显著，其中基因型TT属于保护因素，基因型GG/GT属于独立危险因素; 同时BMI、Hcy也会对血脂异常产生影响。

Abstract

Objective To investigate the relationship between the G894T polymorphism of the endothelial nitric oxide synthase (eNOS) gene and the lipid metabolism in patients with hypertensive disorder complicating pregnancy (HDCP). Methods The 528 cases of HDCP patients admitted to the Xingtai Third Hospital from January 2016 to January 2020 were selected as the research objects, and 128 normal pregnant women during the same period were selected as the control group. The fasting peripheral venous blood of all study subjects in the early morning was collected, and blood lipid indexes, cystatin C (CysC) and uric acid levels and other biochemical index levels were measured. According to the blood lipid level, it was divided into normal blood lipid group and dyslipidemia group. The dyslipidemia group included 4 subgroups ［hyper triglyceride (TG) blood group (TG≥1.70mmol/L), low high-density lipoprotein cholesterol (HDL-C)］ hyper lipidemia group (HDL-C＜1.04mmol/L), high total cholesterol (TC) group (TC≥5.18mmol/L), mixed hyperlipidemia group (TG≥1.70mmol/L, TC≥ 5.18mmol/L)］. In addition, polymerase chain reaction-restriction endonuclease length fragment polymorphism (PCR-RFLP) was used to perform genotyping analysis on the G894T locus of the eNOS gene, which was divided into TT, GT and GG genotypes. The distribution of gene polymorphisms in people with different blood lipid levels was compared, and Logistic regression was used to analyze the influencing factors of dyslipidemia and the relationship between NOS gene G894T polymorphism and dyslipidemia. Results The expected and observed genotypes of GG, GT, TT, eNOS gene G894T locus in the study group and the control group conformed to the Hardy-Weinberg equilibrium law (χ2=0.651, P=0.722; χ2=1.845, P=0.398), and the GG type gene frequency and G allele frequency of the study group were higher than those of the control group, and the TT type gene frequency and T allele frequency of the study group were lower than those of the control group (P<0.05); homocysteine (Hcy), uric acid, C-reactive protein (CRP).The urine microalbumin to creatinine ratio (UACR) level and body mass index(BMI) were higher than those in the normal blood lipid group, and the rate of taking antihypertensive drugs was lower (P<0.05). Dyslipidemia group eNOS gene (G894T) gene GG gene frequency and G allele were higher than normal blood lipid group, TT gene frequency and T allele were lower than normal blood lipid group (P<0.001). The BMI of patients in the low HDL-C group, hyper TG group and mixed hyperlipidemia group was higher than that of the normal blood lipid group (P<0.05); The Hcy level of the mixed hyperlipidemia group was higher than that of the normal blood lipid group (P<0.05). The TT gene frequency and T allele frequency of the low HDL-C group and the mixed hyperlipidemia group were significantly lower than those of the normal blood lipid group, and the GG gene frequency and G allele frequency were higher than the normal blood lipid group (P<0.05). Logistic regression analysis showed that genotype TT was a protective factor for dyslipidemia in patients with HDCP, and genotype GG, high BMI and high Hcy levels were independent risk factors for dyslipidemia. Conclusion There is a significant correlation between the G894T polymorphism of the eNOS gene and dyslipidemia among patients with hypertension in pregnancy. The genotype TT is a protective factor, and the genotype GG/GT is an independent risk factor; at the same time, BMI and Hcy will also affect dyslipidemia.

导出引用

李靖云路运华郑莉霞赵岗刘慧丽. 内皮型一氧化氮合酶基因G894T位点多态性与妊娠期高血压疾病患者脂代谢的相关性[J]. 解剖学报. 2022, 53(6): 737-743 https://doi.org/10.16098/j.issn.0529-1356.2022.06.007

LI Jing-yun LU Yun-hua ZHENG Li-xia ZHAO Gang LIU Hui-li. Relationship between the G894T polymorphism of endothelial nitric oxide synthase gene and lipid metabolism among hypertensive disorder complicating pregnancy patients[J]. Acta Anatomica Sinica. 2022, 53(6): 737-743 https://doi.org/10.16098/j.issn.0529-1356.2022.06.007

中图分类号： R714.246

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