Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India; Department of Biosciences, Integral University, Lucknow, India.
Department of Cytogenetics/Anatomy, All Indian Institute of Medical Sciences (AIIMS), New Delhi, India.
Int J Cardiol. 2019 Sep 15;291:89-95. doi: 10.1016/j.ijcard.2019.03.035. Epub 2019 Mar 19.
Rheumatic heart disease (RHD) is the most serious complication of heart that comprises inflammatory reactions in heart valves. Many studies have demonstrated the contribution of host genetic factors in susceptibility to RHD and many cytokine gene variants have been linked with susceptibility to RHD. We sought to determine the role of genetic variants in IL-1β, STAT3, STAT5B and TLR5 genes in conferring risk of RHD in two cohorts of RHD patients.
The study included 400 echocardiography confirmed RHD patients and 300 controls from North Indian Population. We categorized RHD patients into two sub-groups based on involvement of heart valves, mitral valve lesion alone (MVL), and combined valve lesions including mitral valve (CVL). Genotyping for all the polymorphisms was done using TaqMan /PCR-RFLP methods.
Our results showed that the genotypic frequencies of IL-1β, STAT3, STAT5B andTLR5 genes polymorphisms were significantly associated with RHD risk. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings with RHD risk. In subgroup analysis, STAT3 polymorphism remained significant with MVL in RHD patients.
IL-1β, STAT3, STAT5B and TLR5 genes polymorphism may be useful markers for the identification of individuals with high risk of RHD in the susceptible population.
风湿性心脏病（RHD）是心脏最严重的并发症，包括心脏瓣膜的炎症反应。许多研究表明宿主遗传因素在 RHD 易感性中的作用，许多细胞因子基因变异与 RHD 的易感性有关。我们试图确定 IL-1β、STAT3、STAT5B 和 TLR5 基因中的遗传变异在两个 RHD 患者队列中赋予 RHD 风险的作用。
该研究纳入了 400 名经超声心动图证实的 RHD 患者和 300 名来自印度北部人群的对照者。我们根据心脏瓣膜受累情况将 RHD 患者分为两组：单纯二尖瓣病变（MVL）和包括二尖瓣在内的联合瓣膜病变（CVL）。所有多态性的基因分型均采用 TaqMan/PCR-RFLP 方法进行。
我们的结果表明，IL-1β、STAT3、STAT5B 和 TLR5 基因多态性的基因型频率与 RHD 风险显著相关。为了验证我们的结果，我们在具有相似临床特征的另外 200 例患者中进行了复制研究，结果再次证实了与 RHD 风险的一致性发现。在亚组分析中，STAT3 多态性在 RHD 患者的 MVL 中仍然具有显著性。
IL-1β、STAT3、STAT5B 和 TLR5 基因多态性可能是识别易感人群中 RHD 高危个体的有用标志物。
