The Hypertension Risk Variant Rs820430 Functions as an Enhancer of SLC4A7

The large-scale meta-analysis of genome-wide association study (GWAS) recently identified a genomic locus where the genetic variant at rs820430 was strongly associated with hypertension in Chinese Han population, with its T allele conferred increased risks. However, the biological and disease-relevant mechanisms for this association remain elusive.

A group of 275 participants from rural district of Shandong Province were enrolled, rs820430 was genotyped using genomic DNA with the fluorogenic 5'-nuclease TaqMan allelic discrimination assay system (Applied Biosystems, CA). In vitro experiments were performed in this study, such as luciferase reporter assays, gel mobility shift assays (electrophoretic mobility shift assay), and chromatin immunoprecipitation.

We found the risk T allele of rs820430 was associated with higher SLC4A7 mRNA level in cohort population. Furthermore, we characterized a cis-regulatory mechanism that the T allele of rs820430 distinctively increased c-Fos transcription factor binding, by which leading to increased SLC4A7 expression.

The present study indicated that the disease-associated T allele of a new hypertension risk variant rs820430 linked increased hypertension risk through higher SLC4A7 expression, and rs820430 functioned as an enhancer of SLC4A7 transcription by allele distinctively increased c-Fos transcription factor binding.