Taizhanova Dana, Nurpissova Togzhan, Abildinova Gulshara, Martynyuk Tamilla, Kulmyrzayeva Nazgul, Zholdybayeva Elena
Department of Internal Diseases, Karaganda Medical University Non-Commercial Joint Stock Company, Karaganda 100000, Kazakhstan.
Department of Therapy No. 7, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana 010000, Kazakhstan.
Diagnostics (Basel). 2024 Nov 28;14(23):2687. doi: 10.3390/diagnostics14232687.
Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease. The aim of this study was to evaluate the association of polymorphism of the type 2 bone morphogenetic protein receptor gene (BMPR2) with the risk of IPAH development in an ethnic group of Kazakhs. We also describe the clinical and hemodynamic characteristics and outcomes of patients with and without carriers of BMPR2 gene mutations in IPAH. No available research highlights this problem in an ethnic group of Kazakhs.
A total of 53 patients of only Kazakh nationality with IPAH participated in the study. Clinical, functional, and hemodynamic characteristics, as well as the outcome of the disease, were compared among carriers and non-carriers of the BMPR2 mutation.
When receiving IPAH diagnosis, the average age of patients was 40.0 (32.0-48.0) years. Women predominated among the patients (86.8%). Of these, 17 (32.0%) were carriers of the gene mutation, and 36 (68.0%) did not have this mutation. The results of our research demonstrate that the Rs17199249 variant in BMPR2 contributed to increased susceptibility to IPAH. The T allele was associated with an increased risk of IPAH, with T = 75 (70.75%), G = 31 (29.24%), MAF-0.2925, x-0.001, and HWE -0.975. Carriers of the BMPR2 mutation were predominantly women (80.0%), and they had higher pulmonary vascular resistance (8.7-14.9 vs. 5.9-12.6 WU; = 0.038), a low cardiac index (1.9-2.6 vs. 2.3-3.1 L/min per m; = 0.027), and a shorter time to death ( = 0.022).
This is the first study of the genetic causes of IPAH that demonstrates the genetic polymorphism of BMPR2 is associated with an increased risk of IPAH developing with worse hemodynamic parameters and clinical outcomes.
特发性肺动脉高压（IPAH）是一种进行性致命疾病。本研究旨在评估哈萨克族人群中2型骨形态发生蛋白受体基因（BMPR2）多态性与IPAH发生风险的关联。我们还描述了IPAH患者中携带和不携带BMPR2基因突变者的临床、血流动力学特征及预后情况。目前尚无研究关注哈萨克族人群中的这一问题。
本研究共纳入53例仅为哈萨克族的IPAH患者。比较了BMPR2突变携带者与非携带者的临床、功能和血流动力学特征以及疾病预后。
确诊IPAH时，患者的平均年龄为40.0（32.0 - 48.0）岁。患者中女性占多数（86.8%）。其中，17例（32.0%）为基因突变携带者，36例（68.0%）无此突变。我们的研究结果表明，BMPR2基因中的Rs17199249变异导致IPAH易感性增加。T等位基因与IPAH风险增加相关，T = 75（70.75%），G = 31（29.24%），MAF - 0.2925，χ² = 0.001，HWE = 0.975。BMPR2突变携带者以女性为主（80.0%），他们具有更高的肺血管阻力（8.7 - 14.9 vs. 5.9 - 12.6 WU；P = 0.038）、较低的心指数（1.9 - 2.6 vs. 2.3 - 3.1 L/min per m²；P = 0.027）以及更短的死亡时间（P = 0.022）。
这是第一项关于IPAH遗传病因的研究，表明BMPR2基因多态性与IPAH发生风险增加相关，且伴有更差的血流动力学参数和临床预后。
