Lack of influence of sex hormones on Brugada syndrome-associated mutant Nav1.5 sodium channel

Brugada syndrome (BS) is an autosomal dominant disease. The most common causes of BS are loss-of-function mutations occur in the SCN5A gene which encodes the sodium channel protein Nav1.5. BS has a higher incidence rate in males and the underlying mechanisms of the gender inequality are not yet fully understood. Considering sex hormones are among the most important factors behind gender differences and have previously been shown to regulate the activity of multiple cardiac ion channels, we hypothesized that sex hormones also affect Nav1.5 function which lead to BS predominantly affecting males. In this study, we investigate the protein expression level and current of Nav1.5 in the HEK293 cells cotransfected with SCN5A and sex hormone receptor plasmids using both wild-type SCN5A and BS-associated SCN5A channel mutants R878C and R104W. Our findings showed that sex hormones have no effects on the protein expression level and current of the wild-type Nav1.5, neither does it affect the protein expression level and current of BS-associated Nav1.5 mutants R878C and R104W, regardless of homozygous or heterozygous state. Our results suggest that the male preponderance of BS does not arise from the effects of the sex hormones on Nav1.5. Further studies are needed to explain the male preponderance of this disease. (C) 2018 Published by Elsevier Inc.