Trittmann J K, Nelin L D, Zmuda E J, Gastier-Foster J M, Chen B, Backes C H, Frick J, Vaynshtok P, Vieland V J, Klebanoff M A
Ohio Perinatal Research Network, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
Acta Paediatr. 2014 Oct;103(10):e439-43. doi: 10.1111/apa.12717. Epub 2014 Jul 6.
To test the hypothesis that there are single-nucleotide polymorphisms (SNPs) in genes of the l-arginine/nitric oxide pathway associated with pulmonary hypertension (PH) in neonates with bronchopulmonary dysplasia (BPD).
Neonates with BPD were enrolled (n = 140) and clinical characteristics compared between case (BPD + PH) and control (BPD) groups. DNA was isolated from blood leucocytes and assayed for 17 SNPs in l-arginine/nitric oxide pathway genes by Sequenom massarray. Genes included carbamoyl-phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthase, nitric oxide synthase and arginase. SNPs were selected from the National Center for Biotechnology Information database for their putative functionality. Calculated minor allele frequencies (MAF) of cases and controls were compared using χ2 and logistic regression.
Of the 140 patients with BPD, 26% had echocardiographic evidence of PH. Ventilation days were longer for cases than controls (mean 31 vs. 15 days, p < 0.05). Of the 17 SNPs, rs2781666 in arginase I gene was less common in cases (MAF = 0.23) than controls (MAF = 0.37, p = 0.04). The odds of PH decreased by 43% (p = 0.047) for each copy of the SNP minor allele in arginase I gene in patients with BPD.
Arginase I SNP (rs2781666) may be associated with protection against pulmonary hypertension in preterm neonates with BPD.
检验以下假设，即支气管肺发育不良（BPD）新生儿中，与肺动脉高压（PH）相关的L-精氨酸/一氧化氮途径基因存在单核苷酸多态性（SNP）。
纳入BPD新生儿（n = 140），比较病例组（BPD + PH）和对照组（BPD）的临床特征。从血液白细胞中提取DNA，通过Sequenom质谱分析法检测L-精氨酸/一氧化氮途径基因中的17个SNP。基因包括氨甲酰磷酸合成酶、鸟氨酸转氨甲酰酶、精氨琥珀酸合成酶、一氧化氮合酶和精氨酸酶。根据其假定功能从美国国立生物技术信息中心数据库中选择SNP。使用χ2检验和逻辑回归比较病例组和对照组计算出的次要等位基因频率（MAF）。
140例BPD患者中，26%有PH的超声心动图证据。病例组的通气天数比对照组更长（平均31天对15天，p < 0.05）。在17个SNP中，精氨酸酶I基因中的rs2781666在病例组中的出现频率（MAF = 0.23）低于对照组（MAF = 0.37，p = 0.04）。BPD患者中，精氨酸酶I基因SNP次要等位基因的每一个拷贝使PH的发生几率降低43%（p = 0.047）。
精氨酸酶I SNP（rs2781666）可能与BPD早产儿预防肺动脉高压有关。
