Class II human leukocyte antigen (HLA) molecules predisposition has been proposed to affect RHD, and different HLA alleles have been reported to be associated with RHD susceptibility in different ethnic populations (50–55) while alterations at the C4 complement factor (56), TGF-β1 (49), mannose binding protein, and FcR loci may be pathogenic (13, 57). The gene discussed is C4A; the disease is rheumatic heart disease.