Patterns of Gene Expression in the Ductus Arteriosus Are Related to Environmental and Genetic Risk Factors for Persistent Ductus Patency
Patterns of Gene Expression in the Ductus Arteriosus Are Related to Environmental and Genetic Risk Factors for Persistent Ductus Patency
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DOI：
10.1203/00006450-201011001-00571
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发表时间：
2010-10-01
影响因子：
3.6
通讯作者：
Clyman, Ronald I.
中科院分区：
文献类型：
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作者：
Waleh, Nahid;Hodnick, Ryan;Clyman, Ronald I.
三个独立的危险因素（未成熟妊娠、缺乏产前糖皮质激素暴露和TFAP2B基因rs2817399(A)等位基因的存在）与前列腺素抑制期间无法关闭的动脉导管未闭（pda）有关。我们假设这三个因素可能会影响一组共同的基因，这些基因会增加出生后持久性PDA的风险。我们研究了足月、早产和糖皮质激素处理的早产胎儿的狒狒导管，发现未成熟妊娠和产前糖皮质激素暴露缺失都会降低参与氧诱导收缩的钙和钾通道基因以及磷酸二酯酶基因（调节cAMP/cGMP信号）的RNA表达。从人类妊娠中期获得的导管对TFAP2B多态性进行基因分型。当rs2817399(A)等位基因存在时，也与钙和钾通道基因的表达减少有关。相比之下，与出生后PDA发病率无关的另外两个TFAP2B多态性rs2817419(G)和rs2635727(T)等位基因对RNA表达没有影响。综上所述，三个钙钾通道基因（cacnag /alpha1G、CACNB2/ cal - β 2和KCNA2/Kv1.2）同样受到PDA危险因素的影响。我们推测这些通道可能在前列腺素抑制期间关闭早产导管中发挥重要作用，并可能是未来药物操作的潜在靶点。（儿科研究68:292-297,2010）
Three independent risk factors (immature gestation, absence of antenatal glucocorticoid exposure, and presence of the rs2817399(A) allele of the gene TFAP2B) are associated with patent ductus arteriosus (PDAs) that fail to close during prostaglandin inhibition. We hypothesized that these three factors may affect a common set of genes that increase the risk of persistent PDA after birth. We studied baboon ductus from term, preterm, and glucocorticoid-treated preterm fetuses and found that both immature gestation and absence of antenatal glucocorticoid exposure decreased RNA expression of calcium- and potassium-channel genes involved in oxygen-induced constriction, and phosphodiesterase genes (that modulate cAMP/cGMP signaling). Ductus obtained from second trimester human pregnancies were genotyped for TFAP2B polymorphisms. When present, the rs2817399(A) allele also was associated with decreased expression of calcium- and potassium-channel genes. In contrast, alleles of two other TFAP2B polymorphisms, rs2817419(G) and rs2635727(T), which are not related to the incidence of PDA after birth, had no effect on RNA expression. In conclusion, three calcium- and potassium-channel genes (CACNAIG/alpha1G, CACNB2/CaL-beta2, and KCNA2/Kv1.2) were similarly affected by each of the PDA risk factors. We speculate that these channels may play a significant role in closing the preterm ductus during prostaglandin inhibition and may be potential targets for future pharmacologic manipulations. (Pediatr Res 68: 292-297, 2010)