Impact of serotonin transporter gene polymorphism on gut motility in patients with type 2 Diabetes mellitus

Abstract

Background/Aims The pathogenesis of gastrointestinal (GI) symptoms in patients with type 2 diabetes mellitus (T2DM) is yet to be delineated clearly. Serotonin, a monoamine neurotransmitter, resides primarily in the gut and plays a vital role in GI system. However, no study has been documented the role of serotonin and serotonin transporter gene (SLC6A4) polymorphism in the development of GI symptoms in T2DM patients. Methods Three hundred diabetes patients attending diabetes clinic at Postgraduate Institute of Medical Education and Research, Chandigarh, and matched healthy controls were enrolled for this study. Plasma from collected blood sample was used for serotonin measurement by enzyme-linked immunosorbent assay method and buffy coat was used for isolation of DNA by phenol chloroform method. Serotonin transporter gene polymorphism was analyzed by polymerase chain reaction method. Results The frequency of short allele (S) and SS genotype was significantly higher in patients with T2DM than controls and was associated with increased risk of T2DM. The frequency of LS genotype showed an association with protection from the disease. Regarding GI symptoms, 78.2% of patients with constipation showed LL and LS genotypes, and 97.7% of patients with diarrhea had SS genotype. The patients without GI symptoms did not show any association of gut motility with genotype. Furthermore, serotonin was significantly higher in diabetic patients who belonged to SS genotype compared to LS or LL genotype and who presented with diarrhea. Conclusion SS genotypes are prone to develop diarrhea because of faster gut motility resulting from higher serotonin levels as compared to LS and LL genotype in T2DM patients.

Association of the Effect of SLC6A4 Gene Polymorphisms on the Risk of Diabetes‏

“…Studies showed a close relationship between the homozygous allele S and diabetes. It has been observed that the SS genotype is predominant in diabetic patients (26). Another study reported an association between SERT with glucose metabolism, body mass index, and type 2 diabetes.…”

Family Relationships and Alcohol Consumption: Interaction with the Serotonin Transporter Promoter Polymorphism (5-HTTLPR)

“…SLC6A4 is the gene that encodes the serotonin transporter protein and a functional variation in the 5′ promoter region that involves a 44-base pair insertion/deletion is believed to affect expression of the gene [11]. When compared to the L allele, the S allele has reduced transcriptional efficiency [12, 13]. With regard to the relation of the 5-HTTLPR and alcohol use, there are contradictory findings in the literature, but overall, it appears that the S allele is more frequently predisposing to AUD [14].…”