Gupta-Malhotra Monesha, Hashmi Syed Shahrukh, Barratt Michelle S, Milewicz Dianna M, Shete Sanjay
a Department of Pediatric Cardiology , Johns Hopkins All Children's Hospital, Johns Hopkins University , Saint Petersburg , FL , USA.
b Pediatric Research Center, Department of Pediatrics , McGovern Medical School at the University of Texas Health Science Center in Houston , Houston , TX , USA.
Blood Press. 2018 Oct;27(5):289-296. doi: 10.1080/08037051.2018.1463818. Epub 2018 Apr 26.
Determining familial aggregation is an important first step in narrowing the search for disease-causing genes and hence we determined the familial aggregation of EH among first degree relatives of children with EH.
We prospectively enrolled children with EH along with their first degree relatives from a tertiary pediatric hypertension clinic in a large ambulatory care center. We utilized rigorous methodology for blood pressure (BP) measurements and diagnoses of EH to reduce the heterogeneity in the phenotype. For those enrolled, parental BP status was confirmed by in-clinic direct BP measurements. We also enrolled control children without EH along with their first degree relatives from the same pediatric ambulatory center.
In our case-control study of 153 families, the odds of having familial EH was more than 3 times higher among the cases than in controls (OR: 3.63, 95% CI: 1.85-7.12) with 71% of the cases and 41% of the controls reporting familial EH. One parent with EH was seen in 88% of the cases and 52% of the controls (OR: 6.92, 95% CI: 2.68-17.84). The odds of at least one parent (compared to neither) with EH was almost 7-fold higher, and odds of having two parents with EH was 14-fold higher among cases versus controls. The risk of EH did not go back from the first degree relative to the second degree relatives.
We identified familial aggregation with an increased liability of childhood onset EH with parental EH. The risk of childhood onset EH is more than doubled in the presence of EH in both parents versus in a single parent. Prediction for childhood-onset EH is improved by obtaining a family history of EH in the first degree relatives.
确定家族聚集性是缩小致病基因搜索范围的重要第一步,因此我们确定了儿童期原发性高血压(EH)患者一级亲属中EH的家族聚集性。
我们前瞻性地招募了来自大型门诊护理中心三级儿科高血压诊所的儿童期EH患者及其一级亲属。我们采用严格的血压(BP)测量方法和EH诊断方法,以减少表型的异质性。对于入选者,通过门诊直接BP测量确认父母的BP状态。我们还从同一儿科门诊中心招募了无EH的对照儿童及其一级亲属。
在我们对153个家庭的病例对照研究中,病例组中家族性EH的几率比对照组高出3倍多(比值比:3.63,95%可信区间:1.85 - 7.12),71%的病例和41%的对照报告有家族性EH。88%的病例和52%的对照中有一位父母患有EH(比值比:6.92,95%可信区间:2.68 - 17.84)。病例组中至少有一位父母(与无父母相比)患有EH的几率几乎高出7倍,有两位父母患有EH的几率比对照组高出14倍。EH的风险并未从一级亲属回溯到二级亲属。
我们发现了家族聚集性,即父母患有EH会增加儿童期发病EH的易感性。父母双方都患有EH时儿童期发病EH的风险比单亲患有EH时增加了一倍多。通过获取一级亲属的EH家族史,可改善儿童期发病EH的预测。