Researchers´ Profiles - Robert A. Hegele

Dr. Hegele is an endocrinologist who directs a tertiary referral lipid clinic for Southwestern Ontario with about 1000 active patients with illnesses such as diabetes, dyslipidemia and cardiovascular disease. As a human geneticist, his laboratory has focussed on research in dyslipidemia, diabetes, atherosclerosis, hypertension and obesity in Canadian sub-populations and aboriginal communities. His laboratory has discovered the molecular genetic basis of eight human diseases, including hepatic lipase deficiency (MIM 151670), Oji-Cree type 2 diabetes (MIM 142410.0008), familial partial lipodystrophy types 2 and 3 (FPLD2; MIM 151660 and 150330; FPLD3; MIM 604367 and 601487.0012) and mucopolysaccharidosis type IIID (MIM 252940). The discovery of the Oji-Cree diabetes gene is one of the few susceptibility genes for type 2 diabetes so far discovered in aboriginal people. He has also studied (in collaboration with Dr. Kue Young) genetic determinants of cardiovascular disease risk in Inuit. He holds a Canada Research Chair in Human Genetics and a Career Investigator Award from the Heart and Stroke Foundation of Ontario. His first research publication in 1984 was on the topic of abetalipoproteinemia and he has maintained an active interest in the care of patients with this disorder since that time.

Recent Publications:

• Hegele RA, Sun F, Harris SB, Anderson C, Hanley AJG, Zinman B. Genome wide scanning for type 2 diabetes susceptibility in Canadian Oji Cree, using 190 microsatellite markers. J Hum Genet 1999; 44:10 14.
   
• Hegele RA, Cao H, Harris SB, Hanley AJG, Zinman B. The private hepatocyte nuclear factor-1 G319S variant is associated with early onset type 2 diabetes in Canadian Oji-Cree. J Clin Endocrinol Metab 1999; 84:1077 82.
   
• Jeffrey GP, Chakrabarti S, Hegele RA, Adams PC. Polymorphism in intron 4 of HFE may cause overestimation of C282Y homozygote prevalence in haemochromatosis. Nat Genet 1999; 22:325 326.
   
• Hegele RA, Anderson C, Young TK, Connelly PW. G protein beta3 subunit gene splice variant and body fat distribution in Nunavut Inuit. Genome Res 1999; 9:972 977.
   
• Cao H, Hegele RA. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 2000; 9:109-112.
   
• Hegele RA, Cao H, Harris SB, Zinman B, Hanley AJG, Anderson CM. Peroxisome proliferator activated receptor-2 P12A and type 2 diabetes in Canadian Oji-Cree. J Clin Endocrinol Metab 2000; 85: 2014-2019.
   
• Anand SS, Yusuf S, Vuksan V, Devanesen S, Teo KK, Montague PA, Kelemen L, Yi C, Lonn E, Gerstein H, Hegele RA, McQueen M. Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE). Lancet 2000; 356:279-284.
   
• Hegele RA. Premature atherosclerosis associated with monogenic insulin resistance. Circulation 2001; 103:2225-2229.
   
• Mok A, Cao H, Zinman B, Hanley AJ, Harris SB, Kennedy BP, Hegele RA. A single nucleotide polymorphism in protein tyrosine phosphatase PTP-1B is associated with protection from diabetes or impaired glucose tolerance in Oji-Cree. J Clin Endocrinol Metab 2002; 87:724-727.
   
• Triggs-Raine BL, Kirkpatrick RD, Kelly SL, Norquay LD, Cattini PA, Yamagata K, Hanley AJ, Zinman B, Harris SB, Barrett PH, Hegele RA. HNF-1alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community. Proc Natl Acad Sci USA 2002; 99: 4614-4619.
   
• Hegele RA, Cao H, Frankowski C, Mathews ST, Leff T. PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes 2002; 51:3586-3890.
   
• Mok A, Cao H, Hegele RA. Genomic basis of mucopolysaccharidosis type IIID (MIM 252940) revealed by sequencing of GNS encoding N-acetylglucosamine 6-sulfatase. Genomics 2003; 81:1-5.
   
• Bjerregaard R, Young TK, Hegele RA. Low incidence of cardiovascular disease among the Inuit - what is the evidence? Atherosclerosis 2003; 166:351-357.
   
• Wang J, Hegele RA. Genomic basis of cystathioninuria (MIM 219500) revealed by mulitple mutations of cystathionine gamma-lyase (CTH). Human Genetics, 2003; 112:404-408.
   
• Cao H, Hegele RA. LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet 2003; 48: 271-274.
   
• Cao H, van der Veer E, Ban MR, Hanley AJG, Zinman B, Harris SB, Young TK, Pickering JG, Hegele RA. Promoter polymorphism in PCK1 (Phosphoenolpyruvate Carboxykinase Gene) associated with type 2 diabetes mellitus. J Clin Endocrinol Metab 2004; 89:898-903.
   
• Spence JD, Hegele RA. Noninvasive phenotypes of atherosclerosis. Similar windows but Different Views. Stroke 2004; 35:649-653.
   
• Csoka AB, Cao H, Sammak PJ, Constantinescu D, Schatten GP, Hegele RA. Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes. J Med Genet 2004; 41:304-308.
   
• Pollex RL, Khan HM, Connelly PW, Young TK, Hegele RA. The metabolic syndrome in Inuit. Diabetes Care 2004; 27:1517-1518.
   
• Al-Shali KZ, House AA, Hanley AJ, Khan HM, Harris SB, Zinman B, Mamakeesick M, Fenster A, Spence JD, Hegele RA. Genetic variation in PPARG encoding peroxisome proliferator-activated receptor {gamma} associated with carotid atherosclerosis. Stroke 2004; 35:2036-2040.
   
• Al-Shali K, Cao H, Knoers N, Hermus AR, Tack CJ, Hegele RA. A single-base mutation in the peroxisome proliferator-activated receptor gamma4 promoter associated with altered in vitro expression and partial lipodystrophy. J Clin Endocrinol Metab, 2004; 89:5655-5660.
  

email: hegele@robarts.ca