ReproGen-Animal Bioscience Group, Faculty of Veterinary Science, University of Sydney, Camperdown, New South Wales, Australia.
PLoS One. 2013;8(2):e55434. doi: 10.1371/journal.pone.0055434. Epub 2013 Feb 8.
Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.
血管紧张素转换酶（ACE）对血压控制至关重要。人类 ACE 基因包含内含子 Alu 插入/缺失（I/D）多态性，与血清酶水平的变化有关，但其功能机制尚未确定。该多态性还与心血管疾病、2 型糖尿病、肾脏疾病和精英运动员有关。我们对不同身体能力的品种的马的 ACE 基因进行了特征描述。马的基因结构与所有已知哺乳动物 ACE 基因的结构相似。在混合 DNA 中发现的 9 个常见单核苷酸多态性（SNP）被发现以 9 种单倍型遗传。这 3 个 SNP 位于内含子 16 中，与人类 ACE 基因中的 Alu 多态性同源。在该内含子中还发现了一个高度保守的 18 bp 序列，可能是转录因子 Oct-1、HFH-1 和 HNF-3β 的结合位点，并且位于一个更大的高同源区域内。这个假定的调节元件可能有助于调节人类循环酶水平的个体间差异，其功能机制尚未确定。两个马的 SNP 发生在内含子 16 的保守区域内，但它们都没有破坏假定的结合位点。我们提出了一个哺乳动物 ACE 基因的可能调节机制，这是以前未知的。这一进展将允许进一步的分析，从而更好地理解人类 Alu 多态性与酶水平、心血管疾病状态和精英运动员之间的关联的潜在机制。
