Department of Dermatology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Clin Exp Rheumatol. 2023 Aug;41(8):1652-1658. doi: 10.55563/clinexprheumatol/utmjnq. Epub 2023 Jul 4.
Systemic sclerosis (SSc) is a disease with cardiovascular impairment and polymorphisms of the gene coding of angiotensin-converting-enzyme 2 (ACE2) may account for its development. Three single nucleotide polymorphisms of ACE2 (C>G rs879922, G>A rs2285666 and A>G rs1978124) were found to increase the risk for development of arterial hypertension (AH) and cardiovascular (CVS) diseases in different ethnicities. We investigated associations of polymorphisms rs879922, rs2285666 and rs1978124 with the development of SSc.
Genomic DNA was isolated from whole blood. Restriction-fragment-length polymorphism was used for genotyping of rs1978124, while detection of rs879922 and rs2285666 was based on TaqMan SNP Genotyping Assay. Serum level of ACE2 was assayed with commercially available ELISA test.
81 SSc patients (60 women, 21 men) were enrolled. Allele C of rs879922 polymorphism was associated with significantly greater risk for development of AH (OR=2.5, p=0.018), but less frequent joint involvement. A strong tendency to earlier onset of Raynaud's phenomenon and SSc was seen in carriers of allele A of rs2285666 polymorphism. They had lower risk for development of any CVS disease (RR=0.4, p=0.051) and tendency to less frequent gastrointestinal involvement. Women with genotype AG of rs1978124 polymorphism had significantly more frequent digital tip ulcers and lower serum level of ACE2.
Polymorphisms of ACE2 may account for the development of AH and CVS disorders in SSc patients. Strong tendencies to more frequent occurrence of disease specific characteristics distinct to macrovascular involvement will require further studies evaluating significance of ACE2 polymorphisms in SSc.
系统性硬化症（SSc）是一种心血管损伤疾病，血管紧张素转换酶 2（ACE2）基因编码的多态性可能与其发病有关。在不同种族中，ACE2 的三个单核苷酸多态性（C>G rs879922、G>A rs2285666 和 A>G rs1978124）被发现增加了发展为动脉高血压（AH）和心血管（CVS）疾病的风险。我们研究了 ACE2 多态性 rs879922、rs2285666 和 rs1978124 与 SSc 发病之间的关系。
从全血中提取基因组 DNA。采用限制性片段长度多态性方法对 rs1978124 进行基因分型，而 rs879922 和 rs2285666 的检测则基于 TaqMan SNP 基因分型检测。使用商业可得的 ELISA 试剂盒测定 ACE2 的血清水平。
共纳入 81 例 SSc 患者（60 名女性，21 名男性）。rs879922 多态性的等位基因 C 与 AH 发病风险显著增加相关（OR=2.5，p=0.018），但关节受累较少。rs2285666 多态性的等位基因 A 携带者出现雷诺现象和 SSc 的发病倾向更早。他们患任何 CVS 疾病的风险较低（RR=0.4，p=0.051），且胃肠道受累较少。rs1978124 多态性的基因型 AG 的女性数字尖端溃疡更频繁，ACE2 血清水平更低。
ACE2 多态性可能导致 SSc 患者出现 AH 和 CVS 紊乱。具有更频繁发生与大血管受累相关的疾病特异性特征的强烈倾向，需要进一步研究评估 ACE2 多态性在 SSc 中的意义。
