双特异性磷酸酶（DUSP）基因变异可预测支气管肺发育不良患者的肺动脉高压。
Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia.
机构信息
Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, OH, USA.
出版信息
Pediatr Res. 2020 Jan;87(1):81-87. doi: 10.1038/s41390-019-0502-9. Epub 2019 Jul 22.
BACKGROUND
Pulmonary hypertension (PH) in patients with bronchopulmonary dysplasia (BPD) results from vasoconstriction and/or vascular remodeling, which can be regulated by mitogen-activated protein kinases (MAPKs). MAPKs are deactivated by dual-specificity phosphatases (DUSPs). We hypothesized that single-nucleotide polymorphisms (SNPs) in DUSP genes could be used to predict PH in BPD.
METHODS
Preterm infants diagnosed with BPD (n = 188) were studied. PH was defined by echocardiographic criteria. Genomic DNA isolated from patient blood samples was analyzed for 31 SNPs in DUSP genes. Clinical characteristics and minor allele frequencies were compared between BPD-PH (cases) and BPD-without PH (control) groups. Biomarker models to predict PH in BPD using clinical and SNP data were tested by calculations of area under the ROC curve.
RESULTS
In our BPD cohort, 32% (n = 61) had PH. Of the DUSP SNPs evaluated, DUSP1 SNP rs322351 was less common, and DUSP5 SNPs rs1042606 and rs3793892 were more common in cases than in controls. The best fit biomarker model combines clinical and DUSP genetic data with an area under the ROC curve of 0.76.
CONCLUSION
We identified three DUSP SNPs as potential BPD-PH biomarkers. Combining clinical and DUSP genetic data yields the most robust predictor for PH in BPD.
背景
患有支气管肺发育不良（BPD）的患者的肺动脉高压（PH）源于血管收缩和/或血管重塑，这可以通过丝裂原活化蛋白激酶（MAPKs）进行调节。MAPKs 可被双特异性磷酸酶（DUSPs）失活。我们假设 DUSP 基因中的单核苷酸多态性（SNPs）可用于预测 BPD 中的 PH。
方法
研究了被诊断患有 BPD 的早产儿（n=188）。通过超声心动图标准定义 PH。从患者的血液样本中提取基因组 DNA，分析 DUSP 基因中的 31 个 SNPs。比较 BPD-PH（病例）和 BPD-无 PH（对照）组之间的临床特征和次要等位基因频率。使用临床和 SNP 数据通过计算 ROC 曲线下的面积来测试预测 BPD 中 PH 的生物标志物模型。
结果
在我们的 BPD 队列中，有 32%（n=61）患有 PH。在所评估的 DUSP SNPs 中，DUSP1 SNP rs322351 较少，DUSP5 SNPs rs1042606 和 rs3793892 在病例中比在对照组中更为常见。最佳拟合的生物标志物模型结合了临床和 DUSP 遗传数据，ROC 曲线下的面积为 0.76。
结论
我们确定了三个 DUSP SNPs 作为潜在的 BPD-PH 生物标志物。结合临床和 DUSP 遗传数据可提供预测 BPD 中 PH 的最稳健的预测因子。
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