In this retrospective study, the case cohort with GERD refractory to omeprazole treatment ≥40 mg/day for a minimum of 8 weeks showed an association with CYP2C:TG homozygotes (TG/TG), but not CYP2C19*17 homozygotes (UMs), CYP2C:TG heterozygotes, overall CYP2C19*17 alleles, or overall CYP2C:TG haplotypes. Here, CYP2C19 is linked to gastroesophageal reflux disease.