WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The SCN1A gene encodes the α subunit of the neuronal voltage‐gated sodium channel, which is a target for carbamazepine and other antiepileptic drugs (AEDs). • Recent studies have demonstrated that a common polymorphism of SCN1A IVS5‐91 G > A was associated with carbamazepine and phenytoin use in daily practice. • However, it has not been determined whether the polymorphism affects carbamazepine or other AED responsiveness. WHAT THIS STUDY ADDS • This study demonstrated a significant association between the SCN1A IVS5‐91 AA genotype and carbamazepine‐resistant epilepsy, while the AA genotype did not affect carbamazepine use. AIMS To establish whether the SCN1A IVS5‐91 G > A polymorphism of the SCN1A gene, which encodes the neuronal sodium channel α subunit, affects responsivenss to the antiepileptic drugs (AEDS) carbamazepine and/or phenytoin. METHODS SCN1A IVS5‐91 G > A polymorphism was genotyped in 228 Japanese epileptic patients treated with AEDs. The association between AED responsiveness and the polymorphism was estimated by logistic regression analysis, adjusting for clinical factors affecting the outcome of AED therapy. RESULTS The frequency of the AA genotype was significantly higher in carbamazepine‐resistant patients (odds ratio, 2.7; 95% confidence interval (CI), 1.1, 7.1) and was insignificantly higher in AED‐resistant patients. CONCLUSIONS This is the first report demonstrating an association between the SCN1A polymorphism and carbamazepine‐resistant epilepsy.

A cooperative role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and superoxide dismutase 2 (SOD2) to maintain the vascular function has recently been demonstrated in nitrate tolerance. The present study examined whether the combination of low enzyme-activity variants of ALDH2 and SOD2 increases the risk of hypertension in relation to alcohol consumption. A total of 444 Japanese participants in a health-screening program were evaluated. The risk of hypertension among the individuals harboring both the ALDH2*2 allele and the SOD2 Val/Val genotype was significantly higher in drinkers than in nondrinkers (adjusted odds ratio, 6.22; 95% confidence interval, 2.26-17.1; P<0.001). Among these individuals, the systolic/diastolic blood pressure also increased by 0.24/0.14 mmHg for each 1g/day increase in alcohol consumption (P<0.001/P=0.003). These associations were observed, but the degree was lower among those with the other genotype combinations (0.11/0.10 mmHg; P=0.012/P=0.001). Information about the genetic predisposition to alcohol-related diseases may thus be useful to promote lifestyle modifications for high-risk individuals.

This is the first report to show the impact of the GSTs genotypes on the development of NAFLD. This finding, which should be confirmed in further studies in larger populations, may help to develop a more targeted prevention programme at an early stage for subjects with an increased risk for NAFLD.

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