Distinct regulatory elements of SLC6A14 expression contribute to modification of cystic fibrosis phenotypes.

ABSTRACT: The SLC6A14 gene on chromosome X modifies disease presentation in individuals with cystic fibrosis (CF). Population studies have revealed distinct proximal and distal SNP clusters associated with gastrointestinal and lung phenotypes, respectively. Given the co-localization of cis-eQTLs within the corresponding associated chromosomal regions, where less SLC6A14 expression aligns with improved phenotypic outcomes, we sought to understand the SNP contributions to SLC6A14 expression regulation. Using reporter gene assays, we show that the proximal cluster, aligning with pancreas eQTLs, provides variation in promoter activity that is allele-dependent. The more expansive distal cluster, aligning with primary nasal cell eQTLs, was surveyed and found to harbour an enhancer feature that augmented e

SUBMITTER: Esmaeili M 

PROVIDER: S-EPMC12769681 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature