血管紧张素转换酶基因多态性与儿童青少年原发性高血压左心室肥厚的相关性研究

Association between angiotensin converting enzyme gene polymorphisms and left ventricular hypertrophy in children and adolescents with essential hypertension

目的分析原发性高血压儿童及青少年血管紧张素转换酶(ACE)基因I/D多态性分布特征及其与左心室肥厚(LVH)的相关性。方法病例对照研究。以2022年1月至2023年4月于首都儿科研究所附属儿童医院心血管内科住院、初次诊断未经治疗的144例原发性高血压儿童及青少年为研究对象。采用聚合酶链反应-限制性片段长度多态性方法检测ACE基因多态性。根据显性模型分为DD+DI型组、Ⅱ型组,比较各组间基因频率、基因型频率、临床资料、血浆肾素-血管紧张素-醛固酮(RAAS)水平差异。根据超声心动图结果分为LVH组和非LVH组。通过多因素Logistic回归模型分析LVH的影响因素,ACE基因I/D多态性与原发性高血压儿童及青少年LVH的相关性采用Spearman分析,RAAS各指标与LVH的相关性采用偏相关分析。结果144例患儿中DD、DI和Ⅱ基因型频率分别为11.1%、50.7%和38.2%。D、I等位基因频率为分别36.5%(105/288)、63.5%(183/288)。DD+DI型组(89例)儿童年龄大于Ⅱ型组(55例)(Z=-2.308,P=0.021),两组性别、身高等一般资料比较差异均无统计学意义(均P>0.05)。DD+DI型组LVH的发生率高于Ⅱ型组,差异有统计学意义(χ^(2)=5.230,P=0.022)。RAAS水平中肾素活性与左心室质量指数(r=0.276,P=0.002)和相对室壁厚度(r=0.247,P=0.006)呈正相关。多因素Logistic回归分析表明DD+DI型(OR=5.678,95%CI:1.623~19.872)和体重指数(BMI)(OR=1.124,95%CI:1.024~1.233)均是原发性高血压儿童及青少年发生LVH的危险因素(均P<0.05)。结论ACE基因I/D多态性与LVH的发生密切相关,DD+DI基因型及BMI是原发性高血压儿童及青少年发生LVH的独立危险因素。

Objective To examine the distribution features of angiotensin converting enzyme(ACE)gene I/D polymorphisms and their correlation with left ventricular hypertrophy(LVH)in children and adolescents with essential hypertension.Methods This was a case-control study.One hundred and forty-four children and adolescents who were diagnosed with essential hypertension but received no treatment at the Department of Cardiology,Children′s Hospital,Capital Institute of Pediatrics from January 2022 to April 2023 were recruited.ACE gene polymorphisms were detected using the polymerase chain reaction-restriction fragment length polymorphism method.Patients were divided into the DD+DI genotype group and the Ⅱ genotype group according to the dominant model,and the differences in gene frequencies,genotype frequencies,clinical data,and plasma renin-angiotensin-aldosterone system(RAAS)levels were compared between the two groups.In addition,according to the echocardiographic findings,patients were divided into the LVH and non-LVH groups.The risk factors of LVH were analyzed using the multivariate Logistic regression model.The correlation of ACE gene I/D polymorphisms with LVH in children and adolescents with essential hypertension was evaluated using the Spearman analysis.The correlation between plasma RAAS levels and LVH was assessed using the partial correlation analysis.Results The frequencies of DD,DI and Ⅱ genotypes in 144 patients were 11.1%,50.7%and 38.2%,respectively.The frequency of the D and I allele was 36.5%(105/288)and 63.5%(183/288)respectively.Patients in the DD+DI genotype group(89 cases)were older than those in the Ⅱ genotype group(55 cases)(Z=-2.308,P=0.021),and there was no statistically significant difference between the two groups in gender and height(all P>0.05).The incidence of LVH in the DD+DI genotype group was higher than that in the Ⅱ genotype group,with a statistically significant difference(χ^(2)=5.230,P=0.022).Renin activity in RAAS levels was positively correlated with left ventricular mass index and relative wall thickness(r=0.276,0.247;P=0.002,0.006).Multivariate Logistic regression analysis showed that both DD+DI genotype(OR=5.678,95%CI:1.623-19.872)and body mass index(BMI)(OR=1.124,95%CI:1.024-1.233)were risk factors for the development of LVH in children and adolescents with essential hypertension(all P<0.05).Conclusions ACE gene I/D polymorphisms are strongly associated with LVH.DD+DI genotype and BMI are independent risk factors for the development of LVH in children and adolescents with essential hypertension.