# Enrichment of rare CFTR variants in Finnish patients with congenital chloride diarrhea

## TL;DR

This study finds rare genetic variants in the CFTR gene are more common in Finnish patients with a rare intestinal disorder called congenital chloride diarrhea.

## Contribution

The study identifies specific rare CFTR gene variants enriched in Finnish patients with congenital chloride diarrhea.

## Key findings

- Three intronic CFTR variants (rs17132543, rs2283054, rs76622533) are significantly associated with congenital chloride diarrhea.
- Rare CFTR variants are enriched in chromosomes carrying the Finnish founder mutation for the disease.
- The findings suggest a genetic link between CFTR and congenital chloride diarrhea in the Finnish population.

## Abstract

The autosomal recessive disease congenital chloride diarrhea (CLD), caused by loss-of-function mutations in the solute carrier family 26 member 3 (SLC26A3) gene, shows association with inflammatory bowel disease (IBD). However, it is unclear whether IBD risk is associated with genetic or immune signatures. SLC26A3 interacts with several ion transporters linked to intestinal inflammation, such as cystic fibrosis transmembrane conductance regulator (CFTR) and solute carrier family 9 member 3 (SLC9A3) causing congenital sodium diarrhea. We hypothesized that other epithelial channels affecting intestinal salt balance might modulate CLD phenotype or IBD risk.

We analyzed 495 gene variants within 33 ion transporters among 28 patients with CLD and 44,443 population controls.

We found three intronic variants at or near the CFTR locus (rs17132543, rs2283054 and rs76622533) showing statistically significant (P < 1.42x10-5) associations with CLD.

These data demonstrate enrichment of rare variants at the CFTR locus in chromosomes harboring the Finnish founder mutation for CLD.