J Neurogastroenterol Motil.  2021 Apr;27(2):240-247. 10.5056/jnm20211.

Impact of Serotonin Transporter Gene Polymorphism on Gut Motility in Patients With Type 2 Diabetes Mellitus

Affiliations
  • 1Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  • 2Department of Biochemistry, All India Institute of Medical Sciences Rishikesh, Uttarakhand, India
  • 3Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

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.

Keyword

Alleles; Diabetes mellitus; type 2; Polymorphism; genetic; SLC6A4 protein; human; Serotonin plasma membrane transport proteins
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