Low Copy Number of the Salivary Amylase Gene (AMY1) Is Associated with Obesity, Dyslipidemia, and Chronic Low-Grade Inflammation but Not Insulin Sensitivity and Secretion

AbstractIntroductionWhen compared to other primates, humans elicit a large variation in the copy number for the salivary amylase gene, AMY1. This variation can range from 2 to 17 copies. The AMY1 gene is responsible for coding for salivary amylase, an enzyme needed to catalyze the hydrolysis of starch molecules into smaller sugars. AMY1 copy number correlates with the amount and activity of salivary amylase. Few studies have investigated the effect of amylase copy number on fasting and postprandial glucose levels. The aim was first to investigate the association between AMY1 copy numbers and fasting glucose in an observational study, and secondly to investigate the difference in postprandial effect of high-starch meals in individuals with either high or low AMY1 copy numbers.Materials and methodsFor the observational study, we used data from 436 participants from the Malmö Offspring Study (MOS) cohort whom have been genotyped for AMY1. For the meal study (conducted during May 2019), we used genotype-based-recall to recruit 24 participants from the observational study of the MOS cohort: 12 with low AMY1 copy number (from the lowest 20%) and 12 with high AMY1 copy numbers (from the highest 20%). Each subject will be served a breakfast meal of white wheat bread on two separate test days: one containing 40 g and the other containing 80 g of carbohydrates (mainly starch). Blood samples will then be taken at various time points to investigate postprandial glucose and insulin responses.ResultsWhen using linear regression analyses adjusting for age and sex, no significant association between AMY1 copy number and fasting glucose was observed (p = 0.23). However, there was a difference (p = 0.05) in fasting glucose levels between the lowest (2–4 copy numbers: 5.31 mmol/L; 95% CI: 5.13–5.50) and highest (10–16 copy numbers: 5.57 mmol/L; 95% CI: 5.39–5.75) copy number groups. The results for the meal study will be obtained in June 2019 and be presented at the conference.DiscussionOur findings of higher fasting glucose among the group with more than 10 AMY1 copy numbers is the first study to find this and needs to be replicated in other populations.

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Pretreatment Prevotella-to-Bacteroides ratio and salivary amylase gene copy number as prognostic markers for dietary weight loss

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa007 ◽

2020 ◽

Vol 111 (5) ◽

pp. 1079-1086 ◽

Cited By ~ 5

Author(s):

Mads F Hjorth ◽

Lars Christensen ◽

Thomas M Larsen ◽

Henrik M Roager ◽

Lukasz Krych ◽

...

Keyword(s):

Weight Loss ◽

Weight Change ◽

Copy Number ◽

Gene Copy Number ◽

Diet Group ◽

Gene Copy ◽

Whole Grain ◽

Amylase Gene ◽

Salivary Amylase ◽

To Receive

ABSTRACT Background The inconsistent link observed between salivary amylase gene copy number (AMY1 CN) and weight management is likely modified by diet and microbiome. Objective Based on analysis of a previously published study, we investigated the hypothesis that interaction between diet, Prevotella-to-Bacteriodes ratio (P/B ratio), and AMY1 CN influence weight change. Methods Sixty-two people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber, whole grain, intrinsic sugars, and starch or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Before subjects were randomly assigned to receive the NND or ADD diet, blood and fecal samples were collected, from which AMY1 CN and P/B ratio, respectively, were determined. Body weight change was described by using linear mixed models, including biomarker [log10(P/B ratio) and/or AMY1 CN] diet-group interactions. Results Baseline means ± SDs of log10(P/B ratio) and AMY1 CN were −2.1 ± 1.8 and 6.6 ± 2.4, respectively. Baseline P/B ratio predicted a 0.99-kg/unit (95% CI: 0.40, 1.57; n = 54; P < 0.001) higher weight loss for those subjects on the NND compared with those on the ADD diet, whereas AMY1 CN was not found to predict weight loss differences between the NND and ADD groups [0.05 kg/CN (95% CI: −0.40, 0.51; n = 54; P = 0.83)]. However, among subjects with low AMY1 CN (<6.5 copies), baseline P/B ratio predicted a 2.12-kg/unit (95% CI: 1.37, 2.88; n = 30; P < 0.001) higher weight loss for the NND group than the ADD group. No such differences in weight loss were found among subjects in both groups with high AMY1 CN [−0.17 kg/unit (95% CI: −1.01, 0.66; n = 24; P = 0.68)]. Conclusions The combined use of low AMY1 CN and pretreatment P/B ratio for weight loss prediction led to highly individualized weight loss results with the introduction of more fiber, whole grain, intrinsic sugars, and starch in the diet. These preliminary observations suggest that more undigested starch reaches the colon in individuals with low AMY1 CN, and that the fate of this starch depends on the gut microbiota composition. This trial was registered at clinicaltrials.gov as NCT01195610.

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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial

Gut ◽

10.1136/gutjnl-2017-314786 ◽

2017 ◽

Vol 68 (1) ◽

pp. 83-93 ◽

Cited By ~ 84

Author(s):

Henrik Munch Roager ◽

Josef K Vogt ◽

Mette Kristensen ◽

Lea Benedicte S Hansen ◽

Sabine Ibrügger ◽

...

Keyword(s):

Body Weight ◽

Insulin Sensitivity ◽

Gut Microbiome ◽

Inflammatory Markers ◽

Dietary Intervention ◽

Short Chain Fatty Acids ◽

Low Grade ◽

Whole Grain ◽

Intestinal Transit Time ◽

Low Grade Inflammation

ObjectiveTo investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality.Design60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed.Results50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye.ConclusionCompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation.Trial registration numberNCT01731366; Results.

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No Evidence for Association of BMI with Salivary Amylase Gene Copy Number in the UK 1958 Birth Cohort

Obesity ◽

10.1002/oby.22565 ◽

2019 ◽

Vol 27 (9) ◽

pp. 1533-1538 ◽

Cited By ~ 4

Author(s):

Nzar A. A. Shwan ◽

John A. L. Armour

Keyword(s):

Birth Cohort ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Amylase Gene ◽

Salivary Amylase ◽

The Uk

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Human Salivary Amylase Gene Copy Number Impacts Oral and Gut Microbiomes

Cell Host & Microbe ◽

10.1016/j.chom.2019.03.001 ◽

2019 ◽

Vol 25 (4) ◽

pp. 553-564.e7 ◽

Cited By ~ 30

Author(s):

Angela C. Poole ◽

Julia K. Goodrich ◽

Nicholas D. Youngblut ◽

Guillermo G. Luque ◽

Albane Ruaud ◽

...

Keyword(s):

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Amylase Gene ◽

Salivary Amylase

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Lifestyle intervention improves prothrombotic coagulation profile in individuals at high-risk for type 2 diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab124 ◽

2021 ◽

Author(s):

Sebastian Hörber ◽

Rainer Lehmann ◽

Louise Fritsche ◽

Jürgen Machann ◽

Andreas L Birkenfeld ◽

...

Keyword(s):

Insulin Sensitivity ◽

Lifestyle Intervention ◽

Protein S ◽

Liver Fat ◽

Low Grade ◽

Liver Fat Content ◽

Fat Reduction ◽

Low Grade Inflammation ◽

Pai 1

Abstract Aims Patients with obesity and insulin resistance are at higher risk for arterial and venous thrombosis due to a prothrombotic state. If this is reversible by lifestyle intervention was addressed in the current study and potential underlying associations were elucidated. Subjects and methods One-hundred individuals with impaired glucose tolerance or impaired fasting plasma glucose participated in a 1-year lifestyle intervention, including precise metabolic phenotyping and MRT-based determination of liver fat content as well as a comprehensive analysis of coagulation parameters before and after this intervention. Results During the lifestyle intervention significant reductions in coagulation factor activities (II, VII, VIII, IX, XI and XII) were observed. Accordingly, prothrombin time (PT%) and activated partial thromboplastin time (aPTT) were slightly decreased and prolonged, respectively. Moreover, PAI-1, vWF and also protein C and protein S decreased. Fibrinogen, antithrombin, D-Dimer and FXIII remained unchanged. Searching for potential regulators, especially weight loss, but also liver fat reduction, improved insulin sensitivity and decreased low-grade inflammation were linked to favorable changes in hemostasis parameters. Independent of weight loss , liver fat reduction (FII, protein C, protein S, PAI-1, vWF), improved insulin sensitivity (protein S, PAI-1) and reduced low-grade inflammation (PT%, aPTT, FVIII/IX/XI/XII, vWF) were identified as single potential regulators. Conclusions Lifestyle intervention is able to improve a prothrombotic state in individuals at high-risk for type 2 diabetes. Besides body weight, liver fat content, insulin sensitivity and systemic low-grade inflammation are potential mechanisms for improvements in hemostasis and could represent future therapeutic targets.

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