Figure S1. QQ plot of the relationship between expected and observed distribution at baseline. Quantile-quantile plot of baseline data. The relationship between observed (y-axis) and expected (x-axis) distribution. The statistical significance is measured by the negative log of the corresponding p-value for each SNP. (JPEG 92 kb

Alessandro Di Cara (9996)

Anne Hess (5045813)

Armand Valsesia (41439)

Arne Astrup (37672)

Jérôme Carayol (5045810)

Jörg Hager (85462)

Lesli Larsen (5045816)

Trine Blædel (5045819)

Wim Saris (3495548)

Genes & Nutrition

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Additional file 1: of Analysis of circulating angiopoietin-like protein 3 and genetic variants in lipid metabolism and liver health: the DiOGenes study

Table S1. Effect of rs4360730 on BMI, Lipid Profile and Liver Markers. Table S2 Effect of rs9994520 on BMI, Lipid Profile and Liver Markers. (DOCX 21 kb

Additional file 3: of Analysis of circulating angiopoietin-like protein 3 and genetic variants in lipid metabolism and liver health: the DiOGenes study

Abstract Background Angiopoietin-like protein 3 (ANGPTL3), a liver-derived protein, plays an important role in the lipid and lipoprotein metabolism. Using data available from the DiOGenes study, we assessed the link with clinical improvements (weight, plasma lipid, and insulin levels) and changes in liver markers, alanine aminotransferase, aspartate aminotransferase (AST), adiponectin, fetuin A and B, and cytokeratin 18 (CK-18), upon low-calorie diet (LCD) intervention. We also examined the role of genetic variation in determining the level of circulating ANGPTL3 and the relation between the identified genetic markers and markers of hepatic steatosis. Methods DiOGenes is a multicenter, controlled dietary intervention where obese participants followed an 8-week LCD (800 kcal/day, using a meal replacement product). Plasma ANGPTL3 and liver markers were measured using the SomaLogic (Boulder, CO) platform. Protein quantitative trait locus (pQTL) analyses assessed the link between more than four million common variants and the level of circulating ANGPTL3 at baseline and changes in levels during the LCD intervention. Results Changes in ANGPTL3 during weight loss showed only marginal association with changes in triglycerides (nominal p = 0.02) and insulin (p = 0.04); these results did not remain significant after correcting for multiple testing. However, significant association (after multiple-testing correction) were observed between changes in ANGPTL3 and AST during weight loss (p = 0.004) and between ANGPTL3 and CK-18 (baseline p = 1.03 × 10−7, during weight loss p = 1.47 × 10−13). Our pQTL study identified two loci significantly associated with changes in ANGPTL3. One of these loci (the APOA4-APOA5-ZNF259-BUD13 gene cluster) also displayed significant association with changes in CK-18 levels during weight loss (p = 0.007). Conclusion We clarify the link between circulating levels of ANGPTL3 and specific markers of liver function. We demonstrate that changes in ANGPLT3 and CK-18 during LCD are under genetic control from trans-acting variants. Our results suggest an extended function of ANGPTL3 in the inflammatory state of liver steatosis and toward liver metabolic processes

Anne Lundby Hess

Jérôme Carayol

Trine Blædel

Jörg Hager

Alessandro Di Cara

Arne Astrup

Wim H. M. Saris

Lesli Hingstrup Larsen

Armand Valsesia

Directory of Open Access Journals

Analysis of circulating angiopoietin-like protein 3 and genetic variants in lipid metabolism and liver health: the DiOGenes study

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Background: Angiopoietin-like protein 3 (ANGPTL3), a liver-derived protein, plays an important role in the lipid and lipoprotein metabolism. Using data available from the DiOGenes study, we assessed the link with clinical improvements (weight, plasma lipid, and insulin levels) and changes in liver markers, alanine aminotransferase, aspartate aminotransferase (AST), adiponectin, fetuin A and B, and cytokeratin 18 (CK-18), upon low-calorie diet (LCD) intervention. We also examined the role of genetic variation in determining the level of circulating ANGPTL3 and the relation between the identified genetic markers and markers of hepatic steatosis. Methods: DiOGenes is a multicenter, controlled dietary intervention where obese participants followed an 8-week LCD (800 kcal/day, using a meal replacement product). Plasma ANGPTL3 and liver markers were measured using the SomaLogic (Boulder, CO) platform. Protein quantitative trait locus (pQTL) analyses assessed the link between more than four million common variants and the level of circulating ANGPTL3 at baseline and changes in levels during the LCD intervention. Results: Changes in ANGPTL3 during weight loss showed only marginal association with changes in triglycerides (nominal p = 0.02) and insulin (p = 0.04); these results did not remain significant after correcting for multiple testing. However, significant association (after multiple-testing correction) were observed between changes in ANGPTL3 and AST during weight loss (p = 0.004) and between ANGPTL3 and CK-18 (baseline p = 1.03 x 10(-7), during weight loss p = 1.47 x 10(-13)). Our pQTL study identified two loci significantly associated with changes in ANGPTL3. One of these loci (the APOA4-APOA5-ZNF259-BUD13 gene cluster) also displayed significant association with changes in CK-18 levels during weight loss (p = 0.007). Conclusion: We clarify the link between circulating levels of ANGPTL3 and specific markers of liver function. We demonstrate that changes in ANGPLT3 and CK-18 during LCD are under genetic control from trans-acting variants. Our results suggest an extended function of ANGPTL3 in the inflammatory state of liver steatosis and toward liver metabolic processes

Hess, Anne Lundby

Carayol, Jerome

Blaedel, Trine

Hager, Jorg

Di Cara, Alessandro

Astrup, Arne

Saris, Wim H. M.

Larsen, Lesli Hingstrup

Valsesia, Armand

NARCIS 

Carayol, Jérôme

Blædel, Trine

Hager, Jörg

Saris, Wim H M

Copenhagen University Research Information System

English

Analysis of circulating angiopoietin-like protein 3 and genetic variants in lipid metabolism and liver health:the DiOGenes study

https://figshare.com/articles/Additional_file_3_of_Analysis_of_circulating_angiopoietin-like_protein_3_and_genetic_variants_in_lipid_metabolism_and_liver_health_the_DiOGenes_study/6072500

Additional file 1: of Analysis of circulating angiopoietin-like protein 3 and genetic variants in lipid metabolism and liver health: the DiOGenes study

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NARCIS

Copenhagen University Research Information System