妊娠期高血压疾病5,10-亚甲基四氢叶酸还原酶基因多态性与脂代谢的相关性分析

Analysis on the correlation between 5,10-methylenetetrahydrofolate reductase gene polymorphism and lipid metabolism in patients with hypertensive disorder complicating pregnancy

目的探讨妊娠期高血压疾病5,10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与脂代谢的相关性,为临床诊治提供参考依据。方法纳入2016年3月-2018年6月在福建医科大学附属漳州市医院诊断为妊娠期高血压疾病患者624例,采集清晨空腹外周静脉血标本,检测血脂指标、尿酸、胱抑素(Cys C)水平。根据血脂水平分为血脂正常组,血脂异常组,再将血脂异常组进一步分为4个亚组:高三酰甘油(TG)血症组(TG≥1. 70 mmol/L),高总胆固醇(TC)血症组(TC≥5. 18 mmol/L),低高密度脂蛋白胆固醇(HDL-C)血症组(HDL-C <1. 04 mmol/L),混合型高脂血症组(TG≥1. 70 mmol/L、TC≥5. 18 mmol/L)。检测各组患者的MTHFR (C677T)基因分型。结果血脂异常组体质指数(BMI)值、尿酸、C反应蛋白(CRP)、尿微量白蛋白与肌肝比值(UACR)、同型半胱氨酸(Hcy)水平明显高于血脂正常组,差异有统计学意义(均P<0. 05)。血脂异常组MTHFR (C677T)基因的C/C基因频率明显低于血脂正常组,T/T基因频率明显高于血脂正常组,差异有统计学意义(均P<0. 05);血脂异常组C等位基因频率明显低于血脂正常组,T等位基因频率明显高于血脂正常组,差异有统计学意义(均P<0. 05)。高TG血症组、低HDL-C血症组、混合型高脂血症组的BMI值明显高于血脂正常组,差异有统计学意义(均P<0. 05);混合型高脂血症组Hcy水平明显高于血脂正常组,差异有统计学意义(均P<0. 05)。低HDL-C血症组和混合型高脂血症组的C/C基因频率明显低于血脂正常组,T/T基因频率明显高于血脂正常组,差异有统计学意义(均P<0. 05);混合型高脂血症组C等位基因频率明显低于血脂正常组,T等位基因频率明显高于血脂正常组,差异有统计学意义(P<0. 05)。Logistic回归分析显示,基因型C/C是妊娠期高血压疾病患者血脂异常的保护因素,基因型T/T以及高BMI、Hcy是血脂异常的独立危险因素。结论妊娠期高血压疾病MTHFR基因多态性与血脂异常明显相关,其中基因型C/C是保护因素,基因型T/T是独立危险因素;同时也应注意BMI、Hcy对患者血脂异常的影响。

Objective To explore the correlation between 5,10-methylenetetrahydrofolate reductase( MTHFR) gene polymorphism and lipid metabolism in patients with hypertensive disorder complicating pregnancy( HDCP),provide a reference basis for clinical diagnosis and treatment. Methods A total of 624 patients diagnosed as HDCP in Zhangzhou Hospital Affiliated to Fujian Medical University from March 2016 to June 2018 were enrolled,fasting venous blood samples were obtained to detect the levels of blood lipid indexes,uric acid,and cystatin( Cys C). The patients were divided into normal blood lipid group and abnormal blood lipid group according to the levels of blood lipid indexes,then the patients in abnormal blood lipid group were further divided into four subgroups: hypertriglyceridemia group( TG≥1. 70 mmol/L),hypercholesterolemia group( TC≥5. 18 mmol/L),low high-density lipoprotein cholesterol( HDL-C) group( HDL-C<1. 04 mmol/L),and mixed hyperlipidaemia group( TG≥1. 70 mmol/L,TC≥5. 18 mmol/L). Genotypes of MTHFR C677 T in different groups were detected. Results BMI,uric acid,C-reaction protein( CRP),urinary albumin creatinine ratio( UACR),and homocysteine( Hcy) levels in abnormal blood lipid group were statistically significantly higher than those in normal blood lipid group( P<0. 05). The frequency of C/C genotype in MTHFR C677 T gene in abnormal blood lipid group was statistically significantly lower than that in normal blood lipid group,while the frequency of T/T genotype in MTHFR C677 T gene in abnormal blood lipid group was statistically significantly higher than that in normal blood lipid group( P<0. 05). The frequency of C allele in abnormal blood lipid group was statistically significantly lower than that in normal blood lipid group. while the frequency of T allele in abnormal blood lipid group was statistically significantly higher than that in normal blood lipid group( P<0. 05). BMI levels in hypertriglyceridemia group,low HDL-C group,and mixed hyperlipidaemia group were statistically significantly higher than that in normal blood lipid group( P<0. 05). Hcy level in mixed hyperlipidaemia group was statistically significantly higher than that in normal blood lipid group( P<0. 05). The frequencies of C/C genotype in low HDL-C group and mixed hyperlipidaemia group were statistically significantly lower than that in normal blood lipid group,while the frequencies of T/T genotype in low HDL-C group and mixed hyperlipidaemia group were statistically significantly higher than that in normal blood lipid group( P<0. 05). The frequency of C allele in mixed hyperlipidaemia group was statistically significantly lower than that in normal blood lipid group,while the frequency of T allele in mixed hyperlipidaemia group was statistically significantly higher than that in normal blood lipid group( P<0. 05). Logistic regression analysis showed that C/C genotype was a protective factor of dyslipidemia in HDCP patients,T/T genotype,high BMI and Hcy were independent risk factors for dyslipidemia. Conclusion MTHFR gene polymorphism is significantly correlated with dyslipidemia in patients with HDCP,C/C genotype is a protective factor,while T/T genotype is an independent risk factor;more attention should be paid to the effects of BMI and Hcy on dyslipidemia.