Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.
Department of Cardiac Anaesthesia, All India Institute of Medical Sciences, New Delhi, India.
BMC Res Notes. 2021 May 19;14(1):194. doi: 10.1186/s13104-021-05609-5.
Endothelin-1 plays an important role in the pathogenesis of severe pulmonary hypertension. The + 139 'A', adenine insertion variant in 5'UTR of edn1 gene has been reported to be associated with increased expression of Endothelin-1 in vitro. The aim of present study was to explore the association of this variant with the circulating levels of Endothelin-1 in vivo using archived DNA and plasma samples from 38 paediatric congenital heart disease (cyanotic and acyanotic) patients with severe pulmonary hypertension.
The plasma Endothelin-1 levels were highly varied ranging from 1.63 to75.16 pg/ml. The + 139 'A' insertion variant in 5'UTR of edn1 was seen in 8 out of 38 cases with only one acyanotic sample demonstrating homozygosity of inserted 'A' allele at + 139 site (4A/4A genotype). The plasma Endothelin-1 levels in children with homozygous variant 3A/3A genotype were comparable in cyanotic and acyanotic groups. Lone 4A/4A acyanotic sample had ET-1 levels similar to the median value of ET-1 associated with 3A/3A genotype and was absent in cyanotic group presumably due to deleterious higher ET-1 levels. The discussed observations, limited by the small sample size, are suggestive of homozygous adenine insertion variant posing a risk in cyanotic babies with Severe Pulmonary Hypertension.
内皮素-1 在严重肺动脉高压的发病机制中起重要作用。已报道 edn1 基因 5'UTR 中的 + 139 'A'，腺嘌呤插入变异与体外内皮素-1 的表达增加有关。本研究旨在利用存档的 DNA 和血浆样本，从 38 例患有严重肺动脉高压的儿科先天性心脏病（发绀型和非发绀型）患者中探讨该变体与循环内皮素-1 水平之间的关联。
血浆内皮素-1 水平变化很大，范围为 1.63 至 75.16 pg/ml。在 38 例病例中有 8 例出现 edn1 基因 5'UTR 中的 + 139 'A'插入变异，只有 1 例非发绀样本在 + 139 位显示插入 'A'等位基因的纯合性（4A/4A 基因型）。3A/3A 基因型纯合变异的儿童血浆内皮素-1 水平在发绀组和非发绀组之间相似。唯一的 4A/4A 非发绀样本的 ET-1 水平与 3A/3A 基因型相关的 ET-1 中位数相似，且在发绀组中缺失，推测是由于有害的更高 ET-1 水平。由于样本量较小，所讨论的观察结果表明，纯合腺嘌呤插入变体在患有严重肺动脉高压的发绀婴儿中存在风险。
