Angiotensin-Converting Enzyme Gene Polymorphism Influences Gastrointestinal Motility in Type 2 Diabetes Mellitus
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Angiotensin‑Converting Enzyme Gene Polymorphism Influences Gastrointestinal Motility in Type 2 Diabetes Mellitus Aastha Malik1 · Sarama Saha2 · Rajesh Kumar Morya1 · Sanjay Kumar Bhadada3 · Praveen Kumar Singh2 · Satya Vati Rana1,2,4 Received: 3 December 2019 / Accepted: 22 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Uncontrolled diabetes mellitus may affect any part of the gastrointestinal tract (GIT) and impact negatively the quality of life. Angiotensin-converting enzyme (ACE) gene polymorphism can have direct effect on circulating level of ACE which further modifies the degradation of substance P and thus may influence the gut motility. Hence, it could be hypothesised that ACE gene polymorphism would influence the gut motility. An observational analytical study was conducted at PGIMER, Chandigarh. 300 Type2 diabetes mellitus (T2DM) and 200 age and sex matched healthy individuals were enrolled. After taking written consent, 5 ml blood sample was collected for measurement of substance P by ELISA method and for ACE gene polymorphism (insertion[I]/deletion[D]) by polymerase chain reaction. Orocecal transit time (OCTT) was measured using non-invasive lactulose breath test. Out of 300 diabetic patients, 32.7%, 44% and 23.3% belonged to II, ID and DD genotypes, respectively. The frequency of D allele (OR = 1.39) and DD genotype (OR = 2.17) was significantly higher in patients than in controls and was associated with increased risk. Moreover, more number of diabetes patients with constipation (90%) belonged to DD genotype and their OCTT was significantly delayed (166.7 ± 7.3 min) as compared to ID (143.5 ± 4.2 min) or II (121.8 ± 4.9 min) genotype. From this study, it could be concluded that ACE gene polymorphism could be an important contributing factor to influence the gut motility and thus giving rise to the GI symptoms for T2DM patients. Keywords Substance P · Angiotensin-converting enzyme · Polymorphism · Orocecal transit time
* Satya Vati Rana [email protected] Extended author information available on the last page of the article
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Biochemical Genetics
Introduction Diabetes mellitus can influence any part of the gastrointestinal tract. In diabetic patients no particular risk factor has been recognised so far to be responsible for occurrence of gastrointestinal complications (Dedeli et al. 2015). The aetiology of these gastrointestinal (GI) complications is multifactorial and involves both reversible and irreversible processes. With increase in duration, the GI symptoms become more severe and impact negatively the quality of life of individuals with diabetes mellitus (Parkman et al. 2011; Zetine-Löpez et al. 2003). Gut motility is a highly regulated process and takes place at numerous levels. Earlier studies reported that substance P, an 11 amino acid peptide which belongs to tachykinin family, and is widely distributed throughout the neural pathways of mammalian gut and this may influence motility through different tachykinin recepto
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