Genetic variants in rheumatic fever and rheumatic heart disease

• Published in: American journal of medical genetics. Part C, Seminars in medical genetics Seminars in medical genetics, 2020-03, Vol.184 (1), p.159-177
• Main Authors: Muhamed, Babu, Shaboodien, Gasnat, Engel, Mark E.
• Format: Article
• Language: English
• Subjects: Antigens; Biomarkers; Cardiovascular disease; Cardiovascular diseases; Chromosome 6; Chromosomes; Coronary artery disease; Etiology; Female; Fever; Genes; Genetic Association Studies; Genetic diversity; Genetic Predisposition to Disease - genetics; Genetic variance; Genetics; Genomes; Heart diseases; Humans; Interleukin-10 - genetics; Interleukin-6 - genetics; Leukocytes; Male; Nucleotides; Polymorphism, Single Nucleotide - genetics; polymorphisms; Population studies; Rheumatic fever; Rheumatic Fever - genetics; Rheumatic Fever - pathology; Rheumatic heart disease; Rheumatic Heart Disease - genetics; Rheumatic Heart Disease - pathology; Single-nucleotide polymorphism; Therapeutic applications; Transforming Growth Factor beta1 - genetics; Transforming growth factor-b1; Vaccines
• ISSN: 1552-4868; 1552-4876
• DOI: 10.1002/ajmg.c.31773

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.