Genotype-Specific Clinical Response to a Lactose-Free Diet in Adult Patients Evaluated for Lactose Intolerance: Implications for Clinical Assessment.

Background: Lactose intolerance is a common gastrointestinal condition with variable clinical expression, often requiring both clinical and genetic evaluation. While genetic testing identifies genetic predisposition to lactase persistence or non-persistence, the relationship between specific LCT genotypes and clinical response to dietary intervention remains incompletely understood. Aim: To assess the association between LCT genotypes (CC, CT, TT) and symptom improvement following a lactose-free diet in an adult population and to explore the implications for clinical assessment. Methods: A retrospective observational study was conducted including 538 adult patients evaluated for suspected lactose intolerance. Genotype distribution and its association with clinical response to a lactose-free diet were analyzed. Group comparisons were performed using chi-square and non-parametric tests, and logistic regression analysis was used to identify genotype-specific predictors of symptom improvement. Results: The CC genotype was the most prevalent (70.8%), followed by CT (22.9%) and TT (6.3%). No significant differences were observed between genotype groups regarding age, sex, or area of residence. A significant association was identified between LCT genotype and clinical response to lactose restriction (p < 0.001). CT carriers demonstrated the highest rate of symptom improvement (70.7%), followed by CC (43.8%) and TT (17.6%). Logistic regression analysis confirmed higher odds of improvement among CT carriers (OR = 11.28, 95% CI: 4.30-29.56, p < 0.001) and CC carriers (OR = 3.64, 95% CI: 1.47-9.00, p = 0.005) compared with TT individuals. Conclusions: LCT genotype was significantly associated with clinical response to a lactose-free diet. These findings suggest that genetic variation may contribute to differences in symptom response to dietary lactose restriction and support the use of genotypic information as a complementary component of clinical assessment. However, the observed variability in clinical outcomes across genotype groups highlights the multifactorial nature of lactose intolerance and indicates that genetic predisposition alone does not fully explain symptom expression or dietary response.