Associations of carboxypeptidase A1 and gamma-glutamyltransferase 1 genotypes with refractory functional dyspepsia: a potential link to pancreatic pathophysiology and refractory dyspepsia.

BACKGROUND AND AIMS: This study aimed to investigate the associations between SNPs in CPA1, GGT1, and SPINK1 genes and the clinical characteristics of refractory FD including clinical symptoms, pancreatic enzyme abnormalities, and exocrine pancreatic function. METHODS: 97 Patients with FD, 74 refractory FD and 116 control group were recruited. Five pancreatic enzymes were measured. DNA was isolated from blood or duodenal tissue. The SNPs (rs4820599 for GGT1, rs17107315 for SPINK1, and rs77792157 for CPA1) were measured. Endoscopic ultrasonography (EUS) was performed for patients with refractory FD. Pancreatic function was estimated. RESULTS: The distributions of CPA1, GGT1 and SPINK1 genotypes in the refractory FD group were 67GG (90.5%), 7GA (9.5%); 42AA (56.8%), 29AG (39.2%), 3GG (4.0%) and 74AA (100%), respectively. The distributions of CPA1, GGT1 and SPINK1 genotypes in the FD group were 89GG (91.8%), 8GA (8.2%); 53AA (54.6%), 41AG (42.3%), 3GG (3.1%) and 97AA (100%), respectively. There was a numerically significant difference (p = 0.037) in the distribution of CPA1 among the refractory FD, FD, and control group in the view of no correction for three allele distributions. The N-benzoyl-p-aminobenzoic acid (BT-PABA) test, assessed as above or below 60%, showed a numerically significant difference according to GGT1 genotype, with more patients below 60% in the GGT1 AG and GG groups (p = 0.038) considering no correction for three allele distributions. CONCLUSIONS: This study identified a numerically significant association between the CPA1 GA genotype and refractory FD, suggesting a potential role for CPA1 variation in the pathogenesis of refractory FD.