Association of polymorphic variants in serotonin re-uptake transporter gene with Crohn's disease: a retrospective case-control study

AIM: To analyze the distribution of SLC6A4 gene polymorphisms in Crohn’s disease (CD) patients and their association with the disease. METHODS: We evaluated the presence/absence of promoter (5-HTTLPR, rs25531) and intron 2 (STin2 VNTR) polymorphic variants of SLC6A4 gene in a retrospective case-control study including 192 CD patients and 157 healthy controls (HC). Genotyping was performed by polymerase chain reaction. The association of polymorphisms with CD and its clinical subtypes was analyzed using χ(2) and Fisher exact test, binary logistic regression, and haplotype analysis. RESULTS: CD patients and healthy controls had similar sex (88 [45.8%] vs 84 [53.5%] women, respectively; P = 0.154) and age (41.3 ± 12.8 years vs 41.7 ± 8.8 years, respectively, P = 0.091) distribution. Significant differences were observed in the STin2 genotype and allele distribution between CD patients and healthy controls (P = 0.003 and P = 0.002, respectively) and between the corresponding female subgroups (P = 0.004 and P = 0.007, respectively), with a significant negative association of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD (P = 0.013, age- and sex-adjusted odds ratio [OR] 0.5, 95% confidence interval [CI] 0.29-0.86; women: P = 0.006, age-adjusted OR 0.32, 95% CI 0.14-0.72) and a significantly higher S-STin2.12 (5-HTTLPR/rs25531: S-STin2: STin2.12) haplotype distribution in CD patients (P = 0.004, OR 1.62, 95% CI 1.16-2.26). There was no significant association between 5-HTTLRP and rs25531 genotype or allele frequencies and CD and between any SLC6A4 polymorphic loci with clinical CD subtypes. CONCLUSION: STin2 VNTR polymorphism of SLC6A4 gene may contribute to CD pathogenesis.