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Göteborgs universitets publikationer

Low copy number of the salivary amylase gene predisposes to obesity

Författare och institution:
M. Falchi (-); J. S. El-Sayed Moustafa (-); P. Takousis (-); F. Pesce (-); A. Bonnefond (-); Johanna C. Andersson-Assarsson (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); P. H. Sudmant (-); R. Dorajoo (-); M. N. Al-Shafai (-); L. Bottolo (-); E. Ozdemir (-); H. C. So (-); R. W. Davies (-); A. Patrice (-); R. Dent (-); M. Mangino (-); P. G. Hysi (-); A. Dechaume (-); M. Huyvaert (-); J. Skinner (-); M. Pigeyre (-); R. Caiazzo (-); V. Raverdy (-); E. Vaillant (-); S. Field (-); B. Balkau (-); M. Marre (-); S. Visvikis-Siest (-); J. Weill (-); O. Poulain-Godefroy (-); Peter Jacobson (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Lars Sjöström (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); C. J. Hammond (-); P. Deloukas (-); P. C. Sham (-); R. McPherson (-); J. Lee (-); E. S. Tai (-); R. Sladek (-); Lena M S Carlsson (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); A. Walley (-); E. E. Eichler (-); F. Pattou (-); T. D. Spector (-); P. Froguel (-)
Publicerad i:
Nature Genetics, 46 ( 5 ) s. 492-497
Artikel, refereegranskad vetenskaplig
Nature Publishing Group
Sammanfattning (abstract):
Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10-14) and serum enzyme levels (P < 2.20 × 10-16), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy =-0.15 (0.02) kg/m 2; P = 6.93 × 10-10) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10-10). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies. © 2014 Nature America, Inc. All rights reserved.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin
alpha amylase pancreas isoenzyme, alpha amylase saliva isoenzyme, adult, article, body mass, carbohydrate metabolism, controlled study, copy number variation, enzyme blood level, fat mass, female, gene cluster, gene expression, gene identification, genetic association, genetic predisposition, genetic variability, heritability, human, human tissue, insulin release, major clinical study, male, nucleotide sequence, obesity, priority journal, saliva level, subcutaneous fat, adipose tissue, Chinese, enzyme activity, European, gene linkage disequilibrium, gene mapping, gene replication, genetic risk, overlapping gene, principal component analysis, sugar intake, Body Mass Index, Gene Dosage, Genetic Predisposition to Disease, Genomics, Humans, Microarray Analysis, Odds Ratio, Salivary alpha-Amylases
Postens nummer:
Posten skapad:
2015-02-23 16:19
Posten ändrad:
2016-06-10 13:45

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