Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia
Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia
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DOI：
10.1038/s41390-019-0502-9
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Trittmann, Jennifer K.
中科院分区：
文献类型：
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作者：
Chen, Lauren L.;Zmuda, Erik J.;Trittmann, Jennifer K.
背景技术背景：支气管肺发育不良（BPD）患者的肺动脉高压（PH）是由血管收缩和/或血管重构引起的，而血管收缩和/或血管重构可由丝裂原活化蛋白激酶（MAPK）调节。MAPK被双特异性磷酸酶（DUSPs）失活。我们假设DUSP基因的单核苷酸多态性（SNPs）可以用来预测PH在BPD.METHODS：早产儿诊断为BPD（n = 188）进行了研究。根据超声心动图标准定义PH。从患者血液样品中分离的基因组DNA分析DUSP基因中的31个SNP。比较两组患者的临床特征和次要等位基因频率。生物标志物模型预测PH在BPD使用临床和SNP数据进行了测试，通过计算ROC curve.Results下的面积：在我们的BPD队列，32%（n = 61）有PH。的DUSP SNPs评估，DUSP 1 SNP rs322351是不太常见的，和DUSP 5 SNPs rs 1042606和rs3793892是更常见的情况下，比对照组。结合临床和DUSP遗传学数据的最佳拟合生物标志物模型的ROC曲线下面积为0.76。结论：我们确定了3个DUSP SNPs作为BPD-PH的潜在生物标志物。结合临床和DUSP遗传数据，可产生BPD中PH的最稳健预测因子。
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.