Malik Aastha, Saha Sarama, Morya Rajesh K, Bhadada Sanjay K, Rana Satya V
Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Biochemistry, All India Institute of Medical Sciences Rishikesh, Uttarakhand, India.
J Neurogastroenterol Motil. 2021 Apr 30;27(2):240-247. doi: 10.5056/jnm20211.
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.
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.
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.
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.
背景/目的：2型糖尿病（T2DM）患者胃肠道（GI）症状的发病机制尚未完全阐明。血清素作为一种单胺类神经递质，主要存在于肠道中，在胃肠道系统中发挥着至关重要的作用。然而，尚无研究记录血清素及血清素转运体基因（SLC6A4）多态性在T2DM患者胃肠道症状发生中的作用。
本研究纳入了在昌迪加尔医学教育与研究研究生院糖尿病门诊就诊的300例糖尿病患者以及匹配的健康对照者。采集的血样血浆采用酶联免疫吸附测定法检测血清素，血沉棕黄层采用酚氯仿法提取DNA。采用聚合酶链反应法分析血清素转运体基因多态性。
T2DM患者中短等位基因（S）和SS基因型的频率显著高于对照组，且与T2DM风险增加相关。LS基因型的频率显示与疾病保护相关。关于胃肠道症状，78.2%的便秘患者表现为LL和LS基因型，97.7%的腹泻患者为SS基因型。无胃肠道症状的患者未显示肠道运动与基因型之间存在任何关联。此外，与LS或LL基因型且有腹泻症状的糖尿病患者相比，属于SS基因型的糖尿病患者血清素水平显著更高。
与T2DM患者的LS和LL基因型相比，SS基因型因血清素水平较高导致肠道运动加快而更容易发生腹泻。
