Department of Medicine, University of Cape Town, Cape Town, South Africa.
Hatter Institute for Cardiovascular Diseases Research in Africa, Observatory, South Africa.
Am J Med Genet C Semin Med Genet. 2020 Mar;184(1):159-177. doi: 10.1002/ajmg.c.31773. Epub 2020 Feb 21.
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.
风湿性心脏病（RHD）的遗传关联研究有可能有助于我们了解发病机制，并可能为 RHD 病因学的争议提供线索。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志物，并有助于开发疫苗和新的治疗靶点。家族研究的结果以及位于 6p21.3 号染色体上的人类白细胞抗原和基因组其他部位的基因之间观察到的关联，假设了风湿热和 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出与 RHD 易感性相关的遗传变异的证据。使用 HuGENet™系统评价方法，我们评估了 66 项报告 42 个基因的研究。候选基因研究的现有荟萃分析表明，TGF-β1 [rs1800469]和 IL-1β [rs2853550]单核苷酸多态性（SNP）有助于 RHD 的易感性，而 TNF-α [rs1800629 和 rs361525]、TGF-β1 [rs1800470 和 rs4803457]、IL-6 [rs1800795]、IL-10 [rs1800896]与 RHD 无关。然而，RF/RHD 的候选基因研究相对较小，因此缺乏识别可靠和可重复结果的统计能力，强调需要在不同人群中进行大规模多中心研究。
