Justin Guy


Affiliation: Robarts Research Institute
Country: Canada


  1. Iacocca M, Wang J, Sarkar S, Dron J, Lagace T, McIntyre A, et al. Whole-Gene Duplication of PCSK9 as a Novel Genetic Mechanism for Severe Familial Hypercholesterolemia. Can J Cardiol. 2018;34:1316-1324 pubmed publisher
    ..This finding also has therapeutic relevance, as elevated PCSK9 levels may limit the efficacy of high-dose statin therapy and also PCSK9 inhibition. ..
  2. Berberich A, Ho R, Hegele R. Whole genome sequencing in the clinic: empowerment or too much information?. CMAJ. 2018;190:E124-E125 pubmed publisher
  3. Berberich A, Hegele R. The complex molecular genetics of familial hypercholesterolaemia. Nat Rev Cardiol. 2018;: pubmed publisher
  4. Dron J, Wang J, Berberich A, Iacocca M, Cao H, Yang P, et al. Large-scale deletions of the ABCA1 gene in patients with hypoalphalipoproteinemia. J Lipid Res. 2018;59:1529-1535 pubmed publisher
    ..By coupling bioinformatic analyses with next-generation sequencing data, we can successfully assess the spectrum of genetic determinants of many dyslipidemias, including hypoalphalipoproteinemia. ..
  5. Hegele R, Berberich A, Ban M, Wang J, Digenio A, Alexander V, et al. Clinical and biochemical features of different molecular etiologies of familial chylomicronemia. J Clin Lipidol. 2018;12:920-927.e4 pubmed publisher
    ..However, LPL FCS patients have lower postheparin LPL activity and a trend toward higher TGs, whereas low-density lipoprotein cholesterol was higher in non-LPL-FCS patients. ..
  6. Farhan S, Robinson J, McIntyre A, Marrosu M, Ticca A, Loddo S, et al. A novel LIPE nonsense mutation found using exome sequencing in siblings with late-onset familial partial lipodystrophy. Can J Cardiol. 2014;30:1649-54 pubmed publisher
    ..We have identified a novel nonsense mutation in hormone sensitive lipase gene, which likely explains the lipodystrophy phenotype observed in these patients. ..
  7. Dilliott A, Farhan S, Ghani M, Sato C, Liang E, Zhang M, et al. Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease. J Vis Exp. 2018;: pubmed publisher
  8. Ibrahim C, Ban M, Hegele R. The effect of infrequent low-dose rosuvastatin on the lipid profile. Can J Cardiol. 2014;30:1392-5 pubmed publisher
    ..5%), respectively, from baseline (both P < 0.001). Thus, in patients with statin intolerance, infrequent low-dose rosuvastatin significantly improved low-density lipoprotein cholesterol and was well tolerated over the long term. ..
  9. Dubé J, Wang J, Cao H, McIntyre A, Johansen C, Hopkins S, et al. Common low-density lipoprotein receptor p.G116S variant has a large effect on plasma low-density lipoprotein cholesterol in circumpolar inuit populations. Circ Cardiovasc Genet. 2015;8:100-5 pubmed publisher
    ..R730W was associated with neither LDL cholesterol level nor altered in vitro activity. LDLR p.G116S is thus unique: a common dysfunctional variant in Inuit whose large effect on LDL cholesterol may have public health implications. ..

More Information


  1. request reprint
    Hegele R, Oshima J. Phenomics and lamins: from disease to therapy. Exp Cell Res. 2007;313:2134-43 pubmed
  2. Hegele R, Leff T. Unbuckling lipodystrophy from insulin resistance and hypertension. J Clin Invest. 2004;114:163-5 pubmed
    ..Furthermore, the mutant protein appears to directly modulate the renin-angiotensin system in adipose tissue, providing evidence of the pleiotropic effects of PPARgamma. ..
  3. request reprint
    Hegele R, Joy T, Al Attar S, Rutt B. Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism. J Lipid Res. 2007;48:1433-44 pubmed
  4. request reprint
    Hegele R. Monogenic forms of insulin resistance: apertures that expose the common metabolic syndrome. Trends Endocrinol Metab. 2003;14:371-7 pubmed
  5. request reprint
    Hegele R. Phenomics, lipodystrophy, and the metabolic syndrome. Trends Cardiovasc Med. 2004;14:133-7 pubmed
  6. Wang L, McIntyre A, Hegele R. Complex genetic architecture in severe hypobetalipoproteinemia. Lipids Health Dis. 2018;17:48 pubmed publisher
  7. Hegele R, Gidding S, Ginsberg H, McPherson R, Raal F, Rader D, et al. Nonstatin Low-Density Lipoprotein-Lowering Therapy and Cardiovascular Risk Reduction-Statement From ATVB Council. Arterioscler Thromb Vasc Biol. 2015;35:2269-80 pubmed publisher
  8. Kolovic M, Robinson J, Hegele R. Proprietary Considerations in the Use of Cardiovascular Genetic Data. Can J Cardiol. 2016;32:1297-1299 pubmed publisher
    ..Investigators or clinicians who require additional data that is not within the revised tables can still access the data through academic institutions that hold subscriptions to proprietary human mutation databases. ..
  9. Brahm A, Wang G, Wang J, McIntyre A, Cao H, Ban M, et al. Genetic Confirmation Rate in Clinically Suspected Maturity-Onset Diabetes of the Young. Can J Diabetes. 2016;40:555-560 pubmed publisher
    ..Confirmatory genetic testing in patients suspected to have MODY allows for definitive diagnoses which, in turn, may guide management and provide rationales for screening other family members presymptomatically. ..
  10. request reprint
    Wang J, Dron J, Ban M, Robinson J, McIntyre A, Alazzam M, et al. Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically. Arterioscler Thromb Vasc Biol. 2016;36:2439-2445 pubmed
  11. Hegele R, Ginsberg H, Chapman M, Nordestgaard B, Kuivenhoven J, Averna M, et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014;2:655-66 pubmed publisher
  12. Hegele R. Multidimensional regulation of lipoprotein lipase: impact on biochemical and cardiovascular phenotypes. J Lipid Res. 2016;57:1601-7 pubmed publisher
  13. Wang L, Hegele R. Genetics for the Identification of Lipid Targets Beyond PCSK9. Can J Cardiol. 2017;33:334-342 pubmed publisher
    ..Several of these new agents have attained or are closing in on "prime-time readiness" for clinical use in specific situations. ..
  14. request reprint
    Cao H, Hegele R. DNA polymorphism and mutations in CPN1, including the genomic basis of carboxypeptidase N deficiency. J Hum Genet. 2003;48:20-2 pubmed
    ..The frequency of the IVS1 +6C>T polymorphism was 0.051. The reagents described here provide tools for further study of association with clinical and biochemical phenotypes related to allergy and immunity. ..
  15. request reprint
    Hegele R, Zinman B, Hanley A, Harris S, Barrett P, Cao H. Genes, environment and Oji-Cree type 2 diabetes. Clin Biochem. 2003;36:163-70 pubmed
    ..There is also evidence for genetic determination of related metabolic traits in the Oji-Cree. ..
  16. Dron J, Wang J, Low Kam C, Khetarpal S, Robinson J, McIntyre A, et al. Polygenic determinants in extremes of high-density lipoprotein cholesterol. J Lipid Res. 2017;58:2162-2170 pubmed publisher
    ..Multiple types of genetic variants should be considered as contributing factors in patients with extreme dyslipidemia. ..
  17. Dron J, Hegele R. Genetics of Triglycerides and the Risk of Atherosclerosis. Curr Atheroscler Rep. 2017;19:31 pubmed publisher
  18. request reprint
    Hegele R, Cao H, Frankowski C, Mathews S, Leff T. PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes. 2002;51:3586-90 pubmed
    ..Our findings are consistent with the idea that mutant PPARG can underlie the partial lipodystrophy phenotype. ..
  19. Hegele R, Guy J, Ban M, Wang J. NPC1L1 haplotype is associated with inter-individual variation in plasma low-density lipoprotein response to ezetimibe. Lipids Health Dis. 2005;4:16 pubmed
    ..These preliminary pharmacogenetic results suggest that NPC1L1 variation is associated with inter-individual variation in response to ezetimibe treatment. ..
  20. request reprint
    Hegele R, Al Shali K, House A, Hanley A, Harris S, Mamakeesick M, et al. Disparate associations of a functional promoter polymorphism in PCK1 with carotid wall ultrasound traits. Stroke. 2005;36:2566-70 pubmed
    ..The meaning of the opposing associations of PCK1 genotype with IMT and TPV is unclear; more work is required to confirm whether these might be distinct quantitative traits with different biological determinants. ..
  21. Lahiry P, Racacho L, Wang J, Robinson J, Gloor G, Rupar C, et al. A mutation in the serine protease TMPRSS4 in a novel pediatric neurodegenerative disorder. Orphanet J Rare Dis. 2013;8:126 pubmed publisher
    ..This study demonstrates a proof-of-concept whereby combining exome sequencing with homozygosity mapping can find the genetic cause of a rare disease and acquire better understanding of a poorly described protein in human development. ..
  22. Hegele R, Ban M, Hsueh N, Kennedy B, Cao H, Zou G, et al. A polygenic basis for four classical Fredrickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia. Hum Mol Genet. 2009;18:4189-94 pubmed publisher
  23. Hegele R, Cao H, Liu D, Costain G, Charlton Menys V, Rodger N, et al. Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet. 2006;79:383-9 pubmed
    ..2 x 10-5). These novel heterozygous mutations are the first reported for LMNB2, are the first reported among patients with APL, and indicate how sequencing of a reannotated candidate gene can reveal new disease-associated mutations. ..
  24. Iacocca M, Wang J, Dron J, Robinson J, McIntyre A, Cao H, et al. Use of next-generation sequencing to detect LDLR gene copy number variation in familial hypercholesterolemia. J Lipid Res. 2017;58:2202-2209 pubmed publisher
  25. request reprint
    Hegele R, Robinson J. ABC transporters and sterol absorption. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5:31-7 pubmed