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

Batoul Sadat Haerian; Hidayati Mohd Sha'ari; Hui Jan Tan; Choong Yi Fong; Sau Wei Wong; Lai Choo Ong; Azman Ali Raymond; Chong Tin Tan; Zahurin Mohamed

doi:10.1016/j.ygeno.2015.02.001

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

Genomics. 2015 Apr;105(4):229-36. doi: 10.1016/j.ygeno.2015.02.001. Epub 2015 Feb 7.

Authors

Batoul Sadat Haerian¹, Hidayati Mohd Sha'ari², Hui Jan Tan³, Choong Yi Fong⁴, Sau Wei Wong⁵, Lai Choo Ong⁴, Azman Ali Raymond³, Chong Tin Tan⁶, Zahurin Mohamed²

Affiliations

¹ Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: batoolsadat@yahoo.com.
² Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³ Division of Neurology, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
⁴ Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁵ Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
⁶ Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

PMID: 25668517
DOI: 10.1016/j.ygeno.2015.02.001

Abstract

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.

Keywords: Epilepsy; Polymorphism; RORA; RORB; SCN1A; Susceptibility.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Case-Control Studies
Epilepsy / epidemiology
Epilepsy / genetics*
Epistasis, Genetic*
Female
Genetic Predisposition to Disease*
Humans
Malaysia
Male
Middle Aged
NAV1.1 Voltage-Gated Sodium Channel / genetics*
Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics*
Nuclear Receptor Subfamily 1, Group F, Member 2 / genetics
Polymorphism, Single Nucleotide*
Risk
Young Adult

Substances

NAV1.1 Voltage-Gated Sodium Channel
Nuclear Receptor Subfamily 1, Group F, Member 1
Nuclear Receptor Subfamily 1, Group F, Member 2
RORA protein, human
RORB protein, human
SCN1A protein, human