Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes

Clinical Pharmacology and Therapeutics

Volumn 103, Issue 4, 2018, Pages 712-721

  Rotroff, Daniel M ^a   Pijut, Sonja S ^b   Marvel, Skylar W ^a   Jack, John R ^a   Havener, Tammy M ^c   Pujol, Aurora ^d,e   Schluter, Agatha ^d   Graf, Gregory A ^b,f   Ginsberg, Henry N ^g   Shah, Hetal S ^h   Gao, He ^h   Morieri, Mario Luca ^h   Doria, Alessandro ^h   Mychaleckyi, Josyf C ⁱ   McLeod, Howard L ^j   Buse, John B ^k   Wagner, Michael J ^c   Motsinger Reif, Alison A ^a  

^a NORTH CAROLINA STATE UNIVERSITY   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c UNC Hamner Institute for Drug Safety Sciences   (United States)

^d BELLVITGE BIOMEDICAL RESEARCH INSTITUTE IDIBELL   (Spain)

^e INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

^f UNIVERSITY OF KENTUCKY   (United States)

^g Joslin Diabetes Center and Harvard Medical School ^*  (United States)

^h JOSLIN DIABETES CENTER   (United States)

ⁱ UNIVERSITY OF VIRGINIA   (United States)

^j H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^k UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; DUAL SPECIFICITY PHOSPHATASE 3; FENOFIBRATE; FIBROBLAST GROWTH FACTOR 14; GENOMIC DNA; HIGH DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; MINICHROMOSOME MAINTENANCE PROTEIN 6; MITOGEN ACTIVATED PROTEIN KINASE 10; NEUROLIGIN 1; SMAD3 PROTEIN; TRANSCRIPTION FACTOR NRF2; TRANSFORMING GROWTH FACTOR BETA; TRIACYLGLYCEROL; AKR7A3 PROTEIN, HUMAN; ALDEHYDE REDUCTASE; ANTILIPEMIC AGENT; IPO11 PROTEIN, HUMAN; KARYOPHERIN BETA; SMAD3 PROTEIN, HUMAN;

AKR7A3 GENE; ANIMAL EXPERIMENT; ARTICLE; BICC1 GENE; BLACK PERSON; CAUCASIAN; CHOLESTEROL BLOOD LEVEL; CLN8 GENE; CONTROLLED STUDY; CYP4F39 GENE; DARS GENE; DCUN1D4 GENE; DYSLIPIDEMIA; FBXL7 GENE; FOXP1 GENE; GENE; GENE EXPRESSION; GENETIC VARIABILITY; GENOME-WIDE ASSOCIATION STUDY; HARS2 GENE; HECW2 GENE; HSD17B13 GENE; HSD17B3 GENE; HUMAN; IPO11 GENE; LIPOPROTEIN BLOOD LEVEL; LOC102724680 GENE; LOC105372744 GENE; LOC105374394 GENE; MAJOR CLINICAL STUDY; MARCH3 GENE; MAU2 GENE; MIPEP GENE; MOUSE; MRPL12 GENE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NRXN1 GENE; PBX4 GENE; PEX5L GENE; POGZ GENE; PRIORITY JOURNAL; PRRX1 GENE; R3HDM1 GENE; RBM19 GENE; SCGN GENE; SNX7 GENE; ST6GALNAC3 GENE; STX8 GENE; TREATMENT RESPONSE; TRIACYLGLYCEROL BLOOD LEVEL; TRIOBP GENE; ZNF775 GENE; ANIMAL; BLOOD; COMPLICATION; DRUG EFFECT; FEMALE; GENE EXPRESSION PROFILING; GENETICS; LIPID METABOLISM; MALE; METABOLISM; MIDDLE AGED; PHARMACOGENETIC TESTING; PROCEDURES; SIGNAL TRANSDUCTION;

ALDEHYDE REDUCTASE; ANIMALS; BETA KARYOPHERINS; DIABETES MELLITUS, TYPE 2; DYSLIPIDEMIAS; FEMALE; FENOFIBRATE; GENE EXPRESSION PROFILING; GENOME-WIDE ASSOCIATION STUDY; HUMANS; HYPOLIPIDEMIC AGENTS; LIPID METABOLISM; MALE; MICE; MIDDLE AGED; PHARMACOGENOMIC TESTING; SIGNAL TRANSDUCTION; SMAD3 PROTEIN;

EID: 85032957568     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1002/cpt.798     Document Type: Article

References (50)

1. WHO; World Heart Federation; World Stroke Organization, eds. Global atlas on cardiovascular disease prevention and control. Policies, strategies and interventions (World Health Organization, 2011). (2011).
2. Writing Group Members et al. Heart Disease and Stroke Statistics-2016 update: a report from the American Heart Association. Circulation 133, e38–e360 (2016).
3. Saha, S.A., Kizhakepunnur, L.G., Bahekar, A. & Arora, R.R. The role of fibrates in the prevention of cardiovascular disease--a pooled meta-analysis of long-term randomized placebo-controlled clinical trials. Am. Heart J. 154, 943–953 (2007).
4. Jun, M. et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 375, 1875–1884 (2010).
5. Stone, N.J. et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 63(25 Pt B), 2889–2934 (2014).
6. Berglund, L. et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 97, 2969–2989 (2012).
7. ACCORD Study Group et al. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am. J. Cardiol. 99, 27i–33i (2007).
8. Goff, D.C. Jr et al. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am. J. Cardiol. 99, 4i–20i (2007).
9. ACCORD Study Group et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N. Engl. J. Med. 362, 1575–1585 (2010).
10. Gerstein, H.C. et al. Glycemia treatment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am. J. Cardiol. 99, 34i–43i (2007).
11. Ginsberg, H.N. et al. Evolution of the lipid trial protocol of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am. J. Cardiol. 99, 56i–67i (2007).
12. Willer, C.J. et al. Discovery and refinement of loci associated with lipid levels. Nat. Genet. 45, 1274–1283 (2013).
13. ACCORD Study Group et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N. Engl. J. Med. 362, 1563–1574 (2010).
14. Irvin, M.R. et al. A genome-wide study of lipid response to fenofibrate in Caucasians: a combined analysis of the GOLDN and ACCORD studies. Pharmacogenet. Genomics 26, 324–333 (2016).
15. Keech, A. et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366, 1849–1861 (2005).
16. Aslibekyan, S. et al. Variants identified in a GWAS meta-analysis for blood lipids are associated with the lipid response to fenofibrate. PLoS One 7, e48663 (2012).
17. Irvin, M.R. et al. Rare PPARA variants and extreme response to fenofibrate in the Genetics of Lipid-Lowering Drugs and Diet Network Study. Pharmacogenet. Genomics 22, 367–372 (2012).
18. Smith, J.A. et al. The genetic architecture of fasting plasma triglyceride response to fenofibrate treatment. Eur. J. Hum. Genet. 16, 603–613 (2008).
19. Gao, F., Ballantyne, C., Ma, L., Virani, S.S., Keinan, A. & Brautbar, A. Rare LPL gene variants attenuate triglyceride reduction and HDL cholesterol increase in response to fenofibric acid therapy in individuals with mixed dyslipidemia. Atherosclerosis 234, 249–253 (2014).
20. Liu, X. et al. ABCD2 alters peroxisome proliferator-activated receptor α signaling in vitro, but does not impair responses to fenofibrate therapy in a mouse model of diet-induced obesity. Mol. Pharmacol. 86, 505–513 (2014).
21. HPS2-THRIVE Collaborative Group et al. Effects of extended-release niacin with laropiprant in high-risk patients. N. Engl. J. Med. 371, 203–212 (2014).
22. Taylor, F. et al. Statins for the primary prevention of cardiovascular disease. Cochrane Library. (2013).
23. Elias, P.M., Williams, M.L., Holleran, W.M., Jiang, Y.J. & Schmuth, M. Thematic review series: skin lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. J. Lipid Res. 49, 697–714 (2008).
24. Cowart, L.A. et al. The CYP4A isoforms hydroxylate epoxyeicosatrienoic acids to form high affinity peroxisome proliferator-activated receptor ligands. J. Biol. Chem. 277, 35105–35112 (2002).
25. Plafker, K.S. & Plafker, S.M. The ubiquitin-conjugating enzyme UBE2E3 and its import receptor importin-11 regulate the localization and activity of the antioxidant transcription factor NRF2. Mol. Biol. Cell 26, 327–338 (2015).
26. Huang, J., Tabbi-Anneni, I., Gunda, V. & Wang, L. Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G1211-G1221 (2010).
27. Chen, W.D. & Zhang, Y. Regulation of aldo-keto reductases in human diseases. Front. Pharmacol. 3, 35 (2012).
28. Ahmed, M.M. et al. Aldo-keto reductase-7A protects liver cells and tissues from acetaminophen-induced oxidative stress and hepatotoxicity. Hepatology 54, 1322–1332 (2011).
29. Park, J.S., Kang, D.H., Lee, D.H. & Bae, S.H. Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation. Biochem. Biophys. Res. Commun. 465, 542–547 (2015).
30. Tan, C.K., Chong, H.C., Tan, E.H. & Tan, N.S. Getting ‘Smad’ about obesity and diabetes. Nutr. Diabetes 2, e29 (2012).
31. Tan, C.K. et al. Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet. Diabetes 60, 464–476 (2011).
32. Zhu, B., Zhai, J., Zhu, H. & Kyprianou, N. Prohibitin regulates TGF-beta induced apoptosis as a downstream effector of Smad-dependent and -independent signaling. Prostate 70, 17–26 (2010).
33. Kintscher, U. et al. PPARalpha inhibits TGF-beta-induced beta5 integrin transcription in vascular smooth muscle cells by interacting with Smad4. Circ. Res. 91, e35–e44 (2002).
34. Hong, Y.A. et al. Fenofibrate improves renal lipotoxicity through activation of AMPK-PGC-1α in db/db mice. PLoS One 9, e96147 (2014).
35. Yan, T.T. et al. Sex-specific association of rs16996148 SNP in the NCAN/CILP2/PBX4 and serum lipid levels in the Mulao and Han populations. Lipids Health Dis. 10, 248 (2011).
36. Lusis, A.J. & Pajukanta, P. A treasure trove for lipoprotein biology. Nat. Genet. 40, 129–130 (2008).
37. Kathiresan, S. et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat. Genet. 40, 189–197 (2008).
38. Holmen, O.L. et al. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat. Genet. 46, 345–351 (2014).
39. Kurz, T. et al. The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae. Nature 435, 1257–1261 (2005).
40. Uhlén, M. et al. Proteomics. Tissue-based map of the human proteome. Science 347, 1260419 (2015).
41. Su, W. et al. Comparative proteomic study reveals 17β-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease. Proc. Natl. Acad. Sci. USA 111, 11437–11442 (2014).
42. American Diabetes Association. Cardiovascular disease and risk management. Diabetes Care 40 (suppl. 1), S75–S87 (2017).
43. Shah, H.S. et al. Genetic predictors of cardiovascular mortality during intensive glycemic control in type 2 diabetes: findings from the ACCORD Clinical Trial. Diabetes Care 39, 1915–1924 (2016).
44. Graham, H.T. et al. Incorporating concomitant medications into genome-wide analyses for the study of complex disease and drug response. Front. Genet. 7, 138 (2016).
45. Shaun Purcell PLINK version 1.07. (2009).
46. R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org/. (2014).
47. Marvel, S.W. et al. Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial. PeerJ. 5, e3187 (2017).
48. Wu, M.C., Lee, S., Cai, T., Li, Y., Boehnke, M. & Lin, X. Rare-variant association testing for sequencing data with the sequence kernel association test. Am. J. Hum. Genet. 89, 82–93 (2011).
49. Storey, J.D. A direct approach to false discovery rates. J. R. Stat. Soc. Ser. B Stat. Methodol. 64 (Pt 3), 479–498 (2002).
50. Chamberlain, S. & Ushey, K. rsnps: Get SNP (Single-Nucleotide Polymorphism) Data on the Web. (2015).