# G-Protein-Coupled Receptor Class C Group 6 Member A (GPRC6A) and Serine Protease Inhibitor, Kazal Type 1 (SPINK1) Genotypes Associated With Refractory Functional Dyspepsia: A Potential Link to Endosonographic Features

## TL;DR

This study explores how genetic variations in GPRC6A and SPINK1 relate to refractory functional dyspepsia and pancreatic features.

## Contribution

It identifies a potential link between GPRC6A genotype and endosonographic features in refractory functional dyspepsia.

## Key findings

- R-FD patients had significantly higher abnormal pancreatic enzyme levels compared to FD patients.
- The GG genotype of GPRC6A showed significantly higher EUS scores and lobularity in R-FD patients.
- No significant differences in GPRC6A and SPINK1 genotype distribution were found between FD and R-FD groups.

## Abstract

Background: This study aims to determine the associations between single-nucleotide polymorphisms (SNPs) in G-protein-coupled receptor class C group 6 member A​​​​​​​ (GPRC6A) and serine protease inhibitor, Kazal type 1 (SPINK1) genes and the clinical characteristics, including clinical symptoms, pancreatic enzyme abnormalities, and exocrine pancreatic function, with refractory functional dyspepsia (R-FD).

Methods: Around 97 patients with FD and 74 R-FD were recruited. Five pancreatic enzymes were measured. DNA was isolated from blood or duodenal tissues. Endoscopic ultrasonography (EUS) was performed using Olympus EUS (GF-UCT 260; Olympus, Tokyo, Japan) under conscious sedation in patients with R-FD. Exocrine or endocrine pancreatic function was estimated.

Results: Significant differences (p < 0.001) were observed in the ratio of abnormal pancreatic enzyme levels between patients with R-FD and those with FD. However, no significant differences in the distribution of GPRC6A and SPINK1 genotypes were observed in the FD and R-FD groups. EUS score in the GG genotype was significantly higher than in the CC or CG genotypes (p = 0.036 and p = 0.031, respectively) in GPRC6A in R-FD. In addition, the lobularity in GG genotype in GPRC6A in R-FD was also significantly higher (p = 0.023 and p = 0.027, respectively) than that in CC or CG.

Conclusion: Significant differences (p < 0.001) were observed in the ratio of abnormal pancreatic enzyme levels between patients with R-FD and those with FD. GPRC6A genotype was significantly associated with EUS features, and further studies will be needed to clarify the significant association between GPRC6A genotype and EUS score.