Genetic association studies in rheumatic heart disease (RHD) have the potential to contribute toward our understanding of the pathogenetic mechanism, and may shed light on controversies about RHD etiology. Furthermore, genetic association studies may uncover biomarkers that can be used to identify susceptible individuals, and contribute toward developing vaccine and novel therapeutic targets. Genetic predisposition to rheumatic fever and RHD has been hypothesized by findings from familial studies and observed associations between genes located in the human leukocyte antigens on chromosome 6p21.3 and elsewhere in the genome. We sought to summarize, from published Genetic association studies in RHD, evidence on genetic variants implicated in RHD susceptibility. Using HuGENet™ systematic review methods, we evaluated 66 studies reporting on 42 genes. Existing meta-analyses of candidate gene studies suggest that TGF-β1 [rs1800469], and IL-1β [rs2853550] single nucleotide polymorphisms (SNPs) contribute to susceptibility to RHD, whereas the TNF-α [rs1800629 and rs361525], TGF-β1 [rs1800470 and rs4803457], IL-6 [rs1800795], IL-10 [rs1800896] were not associated with RHD. However, candidate gene studies in RF/RHD are relatively small, thus lacking statistical power to identify reliable and reproducible findings, emphasizing the need for large-scale multicenter studies with different populations.

中文翻译：

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风湿热和风湿性心脏病的遗传变异。

风湿性心脏病（RHD）的遗传关联研究有可能有助于我们进一步了解其致病机理，并可能阐明有关RHD病因的争议。此外，遗传关联研究可能会发现可用于识别易感个体的生物标记，并有助于开发疫苗和新型治疗靶标。家族研究的结果以及观察到的位于6p21.3号染色体上的人类白细胞抗原中的基因与基因组中其他位置之间的关联，都假定了风湿热和RHD的遗传易感性。我们试图从已发表的RHD遗传关联研究中总结有关RHD易感性的遗传变异的证据。使用HuGENet™系统评价方法，我们评估了66个关于42个基因的研究报告。现有的候选基因研究的荟萃分析表明，TGF-β1[rs1800469]和IL-1β[rs2853550]单核苷酸多态性（SNPs）对RHD易感性，而TNF-α[rs1800629和rs361525]，TGF-β1 [rs1800470和rs4803457]，IL-6 [rs1800795]，IL-10 [rs1800896]与RHD不相关。但是，RF / RHD中的候选基因研究相对较小，因此缺乏统计能力来确定可靠且可重复的发现，从而强调了针对不同人群进行大规模多中心研究的必要性。IL-10 [rs1800896]与RHD不相关。但是，RF / RHD中的候选基因研究相对较少，因此缺乏统计数据来鉴定可靠且可重复的发现，从而强调了针对不同人群进行大规模多中心研究的必要性。IL-10 [rs1800896]与RHD不相关。但是，RF / RHD中的候选基因研究相对较少，因此缺乏统计数据来鉴定可靠且可重复的发现，从而强调了针对不同人群进行大规模多中心研究的必要性。