Genetic Interaction of H19 and TGFBR1 Polymorphisms with Risk of Epilepsy in a Chinese Population

Abstract

Purpose Long non-coding RNA H19 was highly expressed in the latent period of epilepsy, contributing to apoptosis of hippocampal neurons by targeting let-7b. Transforming growth factor beta receptor 1 (TGFBR1), a target of let-7b, is located on the susceptibility locus for epilepsy. In this context, we investigated the association between tagSNPs in long non-coding RNA H19 and transforming growth factor beta receptor 1 (TGFBR1) rs6478974 and the risk of epilepsy. Patients and Methods The present study consisted of 302 patients with epilepsy and 612 age- and gender-matched controls. The polymorphisms were analyzed using a TaqMan allelic genotyping assay. H19 and TGFBR1 mRNA levels were determined using quantitative real-time polymerase chain reaction. Results The TGFBR1 AT and TT genotypes emerged as a protective factor for the risk of epilepsy (AT vs AA: adjusted OR = 0.59, 95% CI: 0.39–0.89, P = 0.01; TT vs AA: adjusted OR = 0.53, 95% CI: 0.35–0.80, P = 0.002, respectively). The protective effect was also observed in recessive genetic model (adjusted OR = 0.56, 95% CI: 0.38–0.82, P = 0.003). Individuals carrying the rs6478974 TT genotype had lower levels of TGFBR1 mRNA. Moreover, the TCTAT and TCCAA haplotypes emerged as a risk factor for epilepsy and the rs3741219-rs2839698-rs6478974 was associated with an interactive effect on the risk of epilepsy. Conclusion The current study provides evidence of the rs6478974 TT genotype decreasing the susceptibility to epilepsy by reducing the levels of TGFBR1 mRNA.