Interactions between PDA-associated polymorphisms and genetic ancestry alter ductus arteriosus gene expression.
Interactions between PDA-associated polymorphisms and genetic ancestry alter ductus arteriosus gene expression.
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DOI：
10.1038/s41390-021-01506-6
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发表时间：
2022-03
影响因子：
3.6
通讯作者：
Kelsey K
中科院分区：
文献类型：
--
作者：
Clyman RI;Hills NK;Dagle JM;Murray JC;Kelsey K
PTGIS 和 TFAP2B 的 DNA 多态性已被确定为由具有欧洲遗传血统的早产儿组成的人群中动脉导管未闭 (PDA) 的危险因素，但在遗传多样化的人群中则不然。确定 TFAP2B 和 PTGIS 多态性对动脉导管 (DA) 基因表达的影响是否因遗传血统而异。对 273 个人类中期妊娠胎儿的 DA 进行了 TFAP2B 和 PTGIS 多态性以及沿遗传祖先谱系分布的多态性基因分型。 RT-PCR 用于测量 49 个与 DA 闭合相关的候选基因的 RNA 表达。所分析的 DA 中有 17% 具有欧洲血统。在多变量回归分析中，我们发现四个 PDA 相关 TFAP2B 多态性（rs2817399（A）、rs987237（G）、rs760900（C）和 rs2817416（C））与以下基因的表达之间存在一致的关联：EPAS1、CACNB2、ECE1、KCNA2、ATP2A3、EDNRA、EDNRB、 BMP9 和 BMP10，以及 PTGIS 单倍型 rs493694(G)/rs693649(A) 与 PTGIS 和 NOS3 之间。这些变化只发生在有欧洲血统的DA中。除非考虑多态性和遗传祖先之间的相互作用，否则在 DA 样本中没有发现一致的正相关或负相关。当存在于欧洲血统的胎儿中时，PTGIS 和 TFAP2B 多态性与 DA 基因表达的一致变化相关。 PTGIS 和 TFAP2B 的 DNA 多态性已被确定为动脉导管未闭 (PDA) 的危险因素，该人群主要由具有欧洲遗传血统的早产儿组成，但在遗传多样化的人群中则不然。当具有欧洲遗传血统的胎儿的导管中存在相同的 PTGIS 和 TFAP2B 多态性时，它们与导管基因表达的变化相关。除非考虑多态性和遗传祖先之间的相互作用，否则无法发现与基因表达的一致关联。
DNA polymorphisms in PTGIS and TFAP2B have been identified as risk factors for patent ductus arteriosus (PDA) in a population composed of preterm infants with European genetic ancestry but not in more genetically diverse populations. To determine if the effects of TFAP2B and PTGIS polymorphisms on ductus arteriosus (DA) gene expression differ based on genetic ancestry. DA from 273 human second trimester fetuses were genotyped for TFAP2B and PTGIS polymorphisms and for polymorphisms distributing along genetic ancestry lines. RT-PCR was used to measure the RNA expression of 49 candidate genes involved with DA closure. Seventeen percent of the DA analyzed were of European ancestry. In multivariable regression analyses we found consistent associations between four PDA-related TFAP2B polymorphisms (rs2817399(A), rs987237(G), rs760900(C), and rs2817416(C)) and expression of the following genes: EPAS1, CACNB2, ECE1, KCNA2, ATP2A3, EDNRA, EDNRB, BMP9, and BMP10, and between the PTGIS haplotype rs493694(G)/rs693649(A) and PTGIS and NOS3. These changes only occurred in DA with European ancestry. No consistent positive or negative associations were found among DA samples unless an interaction between the polymorphisms and genetic ancestry was taken into account. PTGIS and TFAP2B polymorphisms were associated with consistent changes in DA gene expression when present in fetuses with European ancestry. DNA polymorphisms in PTGIS and TFAP2B have been identified as risk factors for patent ductus arteriosus (PDA) in a population composed primarily of preterm infants with European genetic ancestry but not in more genetically diverse populations. The same PTGIS and TFAP2B polymorphisms are associated with changes in ductus gene expression when present in ductus from fetuses with European genetic ancestry. No consistent associations with gene expression can be found unless an interaction between the polymorphisms and genetic ancestry is taken into account.
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影响因子：
2.9
作者：
Dagle, John M.;Ryckman, Kelli K.;Poulsen, JoAnn
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Clyman, RI
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Clyman, Ronald I.