help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hegele, R. A.
Right arrow Articles by Zinman, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hegele, R. A.
Right arrow Articles by Zinman, B.
The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 10 3373-3377
Copyright © 1997 by The Endocrine Society

Original Studies

Paraoxonase-2 Gene (PON2) G148 Variant Associated with Elevated Fasting Plasma Glucose in Noninsulin-Dependent Diabetes Mellitus1

Robert A. Hegele2, Philip W. Connelly, Stephen W. Scherer, Anthony J. G. Hanley3, Stewart B. Harris, Lap-Chee Tsui and Bernard Zinman

Department of Medicine, St. Michael’s Hospital (R.A.H., P.W.C.); Department of Genetics, The Hospital for Sick Children (S.W.S., L.-C.T.); Samuel Lunenfeld Research Institute and Mount Sinai Hospital (A.J.G.H., B.Z.), University of Toronto, Toronto; and Thames Valley Family Practice Research Unit, University of Western Ontario (S.B.H.), London, Canada

Address all correspondence and requests for reprints to: Robert A. Hegele, M.D., DNA Research Laboratory, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8. E-mail: robert.hegele{at}utoronto.ca

Defining the genetic determinants of NIDDM requires evidence from several complementary approaches, including both linkage and association analyses using both discrete phenotypes and intermediate quantitative traits. We tested for association between common genomic variation in three genes that map to chromosome 7q21-q22 and quantitative traits related to NIDDM in a sample of Oji-Cree. We found that a common genomic variation in codon 148 (alanine or glycine) of the paraoxonase-2 gene (PON2) demonstrated a significant association with a variation in fasting plasma glucose (P < 0.0001). Furthermore, we found a significant association between a variation in fasting plasma glucose and the interaction term comprised of a PON2 codon 148 genetic variation and the presence of noninsulin-dependent diabetes mellitus (NIDDM; P < 0.0001). We then analyzed subjects according to PON2 genotype and NIDDM status. In subjects with NIDDM, the PON2 codon 148 G/G homozygotes had significantly higher mean fasting plasma glucose than subjects with the other two genotypes (P < 0.0001). However, in non-NIDDM subjects, there was no difference in mean fasting plasma glucose among any of the genotypes. There was no association of the PON2 genotype with NIDDM itself, with impaired glucose tolerance, or with other quantitative traits related to NIDDM in this sample. These findings suggest that 1) the PON2 G148 gene variant worsens glycemia in subjects with NIDDM; 2) defining the physiological role of the PON2 gene product would be worthwhile; and 3) genetic factors can modify the severity of clinical phenotypes in subjects with NIDDM.




This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
P. W. Connelly, B. Zinman, G. F. Maguire, M. Mamakeesick, S. B. Harris, R. A. Hegele, R. Retnakaran, and A. J. G. Hanley
Association of the novel cardiovascular risk factors paraoxonase 1 and cystatin C in type 2 diabetes
J. Lipid Res., June 1, 2009; 50(6): 1216 - 1222.
[Abstract] [Full Text] [PDF]

Home page
 Arch. Dis. Child.Home page
T Dwyer, L Blizzard, B Patterson, A-L Ponsonby, K Martin, S Quinn, M M Sale, S M Richards, R Morley, S Rich, et al.
Association between birth weight and adolescent systolic blood pressure in a caucasian birth cohort differs according to skin type, CRH promoter or 11{beta}-HSD2 genotype
Arch. Dis. Child., September 1, 2008; 93(9): 760 - 767.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
M. Marchesani, A. Hakkarainen, T.-P. Tuomainen, J. Kaikkonen, E. Pukkala, P. Uimari, E. Seppala, M. Matikainen, O.-P. Kallioniemi, J. Schleutker, et al.
New Paraoxonase 1 Polymorphism I102V and the Risk of Prostate Cancer in Finnish Men
J Natl Cancer Inst, June 4, 2003; 95(11): 812 - 818.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
X. Wang, Z. Fan, J. Huang, S. Su, Q. Yu, J. Zhao, R. Hui, Z. Yao, Y. Shen, B. Qiang, et al.
Extensive Association Analysis Between Polymorphisms of PON Gene Cluster With Coronary Heart Disease in Chinese Han Population
Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 328 - 334.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Mok, H. Cao, B. Zinman, A. J. G. Hanley, S. B. Harris, B. P. Kennedy, and R. A. Hegele
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., February 1, 2002; 87(2): 724 - 727.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
P. N. Durrington, B. Mackness, and M. I. Mackness
Paraoxonase and Atherosclerosis
Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 473 - 480.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
S. T. Reddy, D. J. Wadleigh, V. Grijalva, C. Ng, S. Hama, A. Gangopadhyay, D. M. Shih, A. J. Lusis, M. Navab, and A. M. Fogelman
Human Paraoxonase-3 Is an HDL-Associated Enzyme With Biological Activity Similar to Paraoxonase-1 Protein but Is Not Regulated by Oxidized Lipids
Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 542 - 547.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
T. K. Young, J. Reading, B. Elias, and J. D. O'Neil
Type 2 diabetes mellitus in Canada's First Nations: status of an epidemic in progress
Can. Med. Assoc. J., September 1, 2000; 163(5): 561 - 566.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. A. Hegele, H. Cao, S. B. Harris, B. Zinman, A. J. G. Hanley, and C. M. Anderson
Peroxisome Proliferator-Activated Receptor-{gamma}2 P12A and Type 2 Diabetes in Canadian Oji-Cree
J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 2014 - 2019.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. A. Hegele, H. Cao, S. B. Harris, A. J. G. Hanley, and B. Zinman
The Hepatic Nuclear Factor-1{alpha} G319S Variant Is Associated with Early-Onset Type 2 Diabetes in Canadian Oji-Cree
J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1077 - 1082.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. A. Hegele, S. B. Harris, B. Zinman, J. Wang, H. Cao, A. J. G. Hanley, L.-C. Tsui, and S. W. Scherer
Variation in the AU(AT)-Rich Element within the 3'-Untranslated Region of PPP1R3 Is Associated with Variation in Plasma Glucose in Aboriginal Canadians
J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3980 - 3983.
[Abstract] [Full Text]

Home page
 StrokeHome page
H. Schmidt, R. Schmidt, K. Niederkorn, A. Gradert, M. Schumacher, N. Watzinger, H.-P. Hartung, and G. M. Kostner
Paraoxonase PON1 Polymorphism Leu-Met54 Is Associated With Carotid Atherosclerosis : Results of the Austrian Stroke Prevention Study
Stroke, October 1, 1998; 29(10): 2043 - 2048.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society