A normal polymorphism site of TLR2 3' untranslated region is related to rheumatic heart disease by up-regulating TLR2 expression.

BACKGROUND: The worldwide incidence of rheumatic heart disease is at least 15.6 million cases and is responsible for around 233,000 deaths per year. The pathogenesis of rheumatic heart disease is complex and involves genetic factors that predispose a person to the development of autoimmune reactions. Although Arg753Gln polymorphism of the TLR2 gene was considered to be related to acute rheumatic fever susceptibility in child, two groups have identified that there were no relations between this Arg753Gln polymorphism and rheumatic heart disease susceptibility.

METHODS: In this study, we scanned the full length 826 bp of 3' untranslated region of TLR2 in a Chinese-Han population and found that the rare allele G of rs35514500 was highly related to rheumatic heart disease.

RESULTS: Results of dual-luciferase assay indicated that this T->G variation weakens the interaction between miR-340 and TLR2 3' untranslated region and up-regulated firefly luciferase expression. Further results about the patients' serum cytokines concentration detection constructed a relationship between G allele of rs35514550 and up-regulated serum IL-6 and TNFα.

CONCLUSIONS: These findings may give insight into understanding of rheumatic heart disease development and create an opportunity to approach the diagnosis and treatment of rheumatic heart disease.