Association of serotonin transporter gene (SERT) polymorphisms with Crohn's disease (CD) phenotypes

Objective: Serotonin (5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis, secretion, vasodilatation and sensory signalling. The serotonin-selective reuptake transporter protein (SERT) terminates the action of 5-HT. Human SERT is encoded by a single gene on chromosome 17q11 ; 2 important polymorphic sites in the SERT gene are: variable number tandem repeats in the gene’s second intron (SERTin2), and an insertion/deletion in the promoter region (SERTPR). Consistent with the effects of 5-HT in the gut, SERT polymorphisms could potentially be involved in the development of different CD phenotypes. The aim of this study was to evaluate the relationship between SERT polymorphisms in CD patients vs. controls. Methods: A total of 193 CD patients (phenotyped in 3 group according to Vienna classification) and 217 control were subjected to genotyping. DNA of all subjects was analysed by polymerase chain reaction (PCR-RT). The association of genetic polymorphic variant SERTPR/rs 25531 and SERTin2 polymorphic loci with the CD patients vs. controls was tested using program SPSS 13.0, UNPHASED ver. 3.0. 10. A test for Hardy – Weinberg equilibrium using Markov chain method implemented in Arlequin ver. 3.0. Chi squared test was used for comparisons of the allele and genotype frequencies among groups ; log likelihood ratio tests were done to compare distributions of the estimated haplotypes among groups. Results: Genotype frequencies of the SERTPR/rs25531 LL, LS and SS in the CD patients (and controls) were 58 (74), 97 (96) and 37 (47), respectively and of the SERTin2 ll, ls and ss genotypes were 76 (77), 91 (92) and 25 (48), respectively. No significant deviations from the expected Hardy– Weinberg proportions were observed in the sample. Pair-wise comparisons of the allele, genotypand haplotype frequencies between CD patients and controls revealed statistical differences for SERT in2 loci ; ss genotype. Conclusion: Polymorphisms of SERT gene could be associated with development of different phenotypes of CD.