Low copy number of the salivary amylase gene predisposes to obesity

Falchi, Mario; Moustafa, Julia S. El-Sayed; Takousis, Petros; Pesce, Francesco; Bonnefond, Amélie; Andersson‐Assarsson, Johanna C.; Sudmant, Peter H.; Dorajoo, Rajkumar; Al-Shafai, Mashael; Bottolo, Leonardo; Özdemir, Erdal; So, Hon Cheong; Davies, R. W.; Patrice, Alexandre; Dent, Robert; Mangino, Massimo; Hysi, Pirro G.; Dechaume, Aurélie; Huyvaert, Marlène; Skinner, Jane; Pigeyre, Marie; Caïazzo, Robert; Raverdy, Violeta; Vaillant, Emmanuel; Field, Sarah; Balkau, Beverley; Marre, Michel; Visvikis‐Siest, Sophie; Weill, Jacques; Poulain‐Godefroy, Odile; Jacobson, Peter; Sjöström, Lars; Hammond, Christopher J.; Deloukas, Panos; Sham, Pak C.; McPherson, Ruth; Lee, Jeannette; Tai, E. Shyong; Sladek, Robert; Carlsson, Lena; Walley, Andrew J.; Eichler, Evan E.; Pattou, François; Spector, Timothy D.; Froguel, Philippe

doi:10.1038/ng.2939

Cited by 215 publications

(305 citation statements)

References 46 publications

(53 reference statements)

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“…It is interesting to note that the evidence for the association between salivary amylase activity and obesity is currently inconclusive. While there is data to suggest that low copy number of AMY1 was correlated with obesity [22][23][24], there is also evidence to the contrary [25]. As obesity is well-known to be associated with impaired glucose tolerance, the former finding is consistent with the data which we have reported in the present paper.…”

Section: Discussionsupporting

confidence: 83%

Anomalous association of salivary amylase secretion with the postprandial glycaemic response to starch

et al. 2016

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Background: This study is an investigation as to whether salivary amylase secretory rates are correlated with the magnitude of postprandial glycaemic responses to starch ingestion in healthy young Malaysian adults. Methods: Fasting unstimulated and stimulated salivary amylase secretory rates were measured and ranked for 54 participants. Subjects (n = 5) with amylase activities below the median and subjects (n = 5) with amylase activities above the median were selected for subsequent carbohydrate challenge tests. Following an overnight fast, the postprandial glycaemic responses of these subjects were assessed to 50 g carbohydrate bolus challenges; glucose (n = 2), maltose (n = 1) and starch (n = 1), tested in random order. Blood glucose concentrations were estimated before each carbohydrate challenge and at half-hour intervals thereafter for 2 h. The magnitude of each glycaemic response was estimated from the area under the curve (AUC). Results: High amylase secretors responded to the consumption of a starch bolus with significantly lower AUCs than low amylase secretors (267 +/− 64 vs. 159 +/− 72 mmol/L*120 min, p = 0.037; mean +/− SD). However, the glycaemic responses to maltose and glucose did not differ significantly between the two groups. These findings confirm that subjects with higher salivary amylase secretory rates have better glycaemic tolerance to a starch challenge than subjects with lower salivary amylase secretory rates. Conclusion: Low amylase secretion should be considered as a potential prognosticator for impaired glucose tolerance to dietary starch in young Malaysian adults.

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Section: Discussionsupporting

confidence: 83%

Anomalous association of salivary amylase secretion with the postprandial glycaemic response to starch

et al. 2016

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“…However, <3% of the phenotypic variance in BMI has been explained by these loci [5], suggesting that other forms of DNA variation (including copy number variation [CNV]) may explain this large missing heritability. In this regard, we recently developed a system biology approach for the identification of potential genedosage effects, combining transcriptomics and GWAS analyses in sibling-pairs discordant for obesity [9]. This approach enabled the identification of a region mapping of both salivary and pancreatic amylase genes (AMY1 and AMY2 [also known as AMY1A and AMY2B], respectively), which was strongly associated with obesity risk and fat mass [9].…”

Section: Introductionmentioning

confidence: 99%

Beneficial effect of a high number of copies of salivary amylase AMY1 gene on obesity risk in Mexican children

et al. 2014

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Aims/hypothesis Childhood obesity is a major public health problem in Mexico, affecting one in every three children. Genome-wide association studies identified genetic variants associated with childhood obesity, but a large missing heritability remains to be elucidated. We have recently shown a strong association between a highly polymorphic copy number variant encompassing the salivary amylase gene (AMY1 also known as AMY1A) and obesity in European and Asian adults. In the present study, we aimed to evaluate the association between AMY1 copy number and obesity in Mexican children. Methods We evaluated the number of AMY1 copies in 597 Mexican children (293 obese children and 304 normal weight controls) through highly sensitive digital PCR. The effect of AMY1 copy number on obesity status was assessed using a logistic regression model adjusted for age and sex. ResultsWe identified a marked effect of AMY1 copy number on reduced risk of obesity (OR per estimated copy 0.84, with the number of copies ranging from one to 16 in this population; p=4.25×10 −6). The global association between AMY1 copy number and reduced risk of obesity seemed to be mostly driven by the contribution of the highest AMY1 copy number. Strikingly, all children with >10 AMY1 copies were normal weight controls. Conclusions/interpretation Salivary amylase initiates the digestion of dietary starch, which is highly consumed in Mexico. Our current study suggests putative benefits of high number of AMY1 copies (and related production of salivary amylase) on energy metabolism in Mexican children.

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“…AMY1: CNVs in AMY1 encoding salivary amylase have been associated with variations in BMI (low copy number associated with higher BMI) in two independent samples. 88 The effect size plotted in Figure 2 (0.75 kg/m 2 ) is based on the maximum possible negative difference in copy number (−5) from the mean of the normal-weight distributions in Falchi et al 88 This effect size is small compared to our estimate, 18 but could contribute to a …”

Section: Fto: Common Single-nucleotide Polymorphisms (Snps)mentioning

confidence: 48%

“…The CNV in AMY1 was investigated in relation to BMI after an initial screen of effects on gene expression in adipose tissue, 88 but the salivary amylase product is also expressed in saliva under the influence of copy number 89 and in various other tissues. The mechanisms linking AMY1 expression and BMI have not been established, but AMY1 is known to have a role in sensory perception of starch in foods as well as being regulated by autonomic nervous system (ANS) activity, 90 providing potential links to and from hypothalamic appetite-regulating centers and therefore possible consistency with the NBH.…”

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confidence: 99%

Future management of human obesity: understanding the meaning of genetic susceptibility

Jenkins¹,

Campbell²

2014

AGG

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Gene-environment interactions are central to the expression of obesity. The condition is strongly heritable (ie, genetic), and most of the variation in obesity levels between countries and between individuals can be explained by the effects of obesogenic environments on individual genetic susceptibilities. The nature of the obesogenic environmental influences is not clear in detail, but they correlate closely with measures of affluence. The causes of variation in genetic susceptibility are also not clearly defined, but their general nature has become clearer. The failure of genome-wide association studies or large linkage studies to identify or replicate causative genetic variants, together with the segregation of obesity-related traits in families, implicates a heterogenetic mechanism in which rare, dominantly or additively expressed genetic variants are responsible for most of common obesity. The search for rare causative variants continues with some successes, but those identified contribute very little to the overall burden and, assuming heterogenetics, there are many more to find. The time when genomic risk factors provide more information than do currently available markers, such as family history, is a long way off. Genomic studies to date have contributed little, if anything, to the prevention and treatment of common obesity and its associated disorders. This contrasts with the obvious and immediate potential implications of the well-established overall genetic basis of obesity, which have not yet been exploited in the clinical or public health arenas. Genomic studies, which have helped to define the genetic basis of common obesity mainly by exclusion, will in the future play an increasingly important role in understanding and managing obesity, but only with parallel studies of the physiological, behavioral, and economic influences. Keywords: obesity phenotypes, obesogenic environment, genomics, pathophysiology, treatment, prevention Background and aimsAccording to the World Health Organization projections, by 2015 about 2.3 billion adults in the world will be overweight and over 700 million will be obese, and economic costing predicts that obesity-related expenditure in USA will approach US$100 billion per annum.1 It is now widely, if not universally, accepted that the rising national and global prevalence of overweight and obesity since the 1980s can be understood as the effects of increasingly obesogenic environments (OEs), which are correlated with measures of affluence and food availability, 2 in genetically predisposed individuals. 3,4 Obesity is assessed by the body mass index (BMI, kg/m 2 ) in most epidemiological and genetic studies, often together with measures of central fat distribution such as waist circumference because of adverse metabolic and health associations. However, neither BMI nor other anthropometric measurements are by themselves sufficiently accurate

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Low copy number of the salivary amylase gene predisposes to obesity

Cited by 215 publications

References 46 publications

Anomalous association of salivary amylase secretion with the postprandial glycaemic response to starch

Anomalous association of salivary amylase secretion with the postprandial glycaemic response to starch

Beneficial effect of a high number of copies of salivary amylase AMY1 gene on obesity risk in Mexican children

Future management of human obesity: understanding the meaning of genetic susceptibility

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