Evidence from familial studies suggests that genetic predisposition may explain susceptibility to Rheumatic heart disease (RHD). However, the genetic studies conducted in RHD have no consensus on the susceptibility gene. We undertook to perform a meta-analysis gene association study in rheumatic fever (RF) and RHD based on the HuGENetMT guidelines.
We sought to include all HLA allele studies that used sequence-specific primers methods, as well as those studies incorporating non-HLA genes studied in RF and RHD. Multiple electronic databases were searched, references identified from bibliographies were sought, and experts and authors of primary studies were also contacted. Strict review inclusion criteria were determined. Random effects meta-analyses were performed; statistical heterogeneity and inconsistency were assessed.
Thirty-one RHD association studies meeting review inclusion criteria were identified from the initial 135 articles ascertained through the search. In all, 27 genes were reported; after an initial review. Among the genetic factors evaluated, RHD appears to be most strongly associated with TNF-α (-308G/A) (OR=1.82, 95% CI [1.01; 3.29]) and HLA-DRB1*15 (OR=0.56, 95%-CI [0.40; 0.78]).
TNF-α and HLA-DRB1*15 are associated with increased susceptibility to RHD. The pooled estimates, however, are based on a small number of studies and thus, this meta-analysis revealed the necessity for large, adequately powered genome-wide association studies to determine genetic susceptibility in RHD.