RORA gene rs12912233 and rs880626 polymorphisms and their interaction with SCN1A rs3812718 in the risk of epilepsy: A case-control study in Malaysia

- RORA rs12912233 was significantly associated with susceptibility to epilepsy in Malaysian Chinese.
- This locus together with RORA rs880626 and SCN1A rs3812718 showed a strong epistatic interaction risk for epilepsy.
- Consistent results of epilepsy, depression and autism data suggest shared common loci of both genes for these disorders.

RAR-related orphan receptors A (RORA) and B (RORB) and voltage-gated sodium channel type 1 (SCN1A) genes play critical roles in the regulation of the circadian clock. Evidence has shown an association of RORA and RORB polymorphisms with susceptibility to autism and depression. Hence, we tested the association of RORA rs12912233, rs16943429, rs880626, rs2290430, and rs12900948; RORB rs1157358, rs7022435, rs3750420, and rs3903529; and SCN1A rs3812718 with epilepsy risk in the Malaysians. DNA was genotyped in 1789 subjects (39% epilepsy patients) by using MassARRAY (Sequenom). Significant association was obtained for rs12912233 in Malaysian Chinese (p = 0.003). Interaction between rs12912233-rs880626 and rs3812718 was associated with the epilepsy risk in the subjects overall (p = 0.001). Results show that RORA rs12912233 alone might be a possible risk variant for epilepsy in Malaysian Chinese, but that, together with RORA rs880626 and SCN1A rs3812718, this polymorphism may have a synergistic effect in the epilepsy risk in Malaysians.