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Clinical and genetic associations with hypertriglyceridemic waist in a Canadian aboriginal population

International Journal of Obesity volume 30, pages 484–491 (2006)Cite this article

Abstract

Objectives:

To determine the prevalence of ‘hypertriglyceridemic waist’ (HTGW) in Oji-Cree, to examine its interaction with hepatic nuclear factor-1α (HNF1A) in association with type 2 diabetes, and to characterize its putative genetic determinants.

Method:

The presence or absence of HTGW was determined in 522 Oji-Cree subjects (223 males, 299 females), ⩾18 years of age, in whom physical measurements and fasting plasma analyte concentrations were gathered, and a 75-g oral glucose tolerance test was administered, as part of a cross-sectional study. Subjects were genotyped for HNF1A codon 319, angiotensinogen (AGT) codons 174 and 235, G-protein β3-subunit (GNB3) nucleotide 825, fatty acid-binding protein (FABP2) codon 54, nucleotides −455 and −482 of the apolipoprotein (apo) C-III (APOC3) promoter, and a 5-bp insertion/deletion polymorphism within the 3′-untranslated region of protein phosphatase 1 regulatory subunit 3 (PPP1R3).

Results:

The unadjusted prevalence of HTGW in Oji-Cree adults was 20.5%, with more males affected than females (27.8 vs 15.1%, P=0.0004). Logistic regression analysis, adjusted for age and gender, showed type 2 diabetes was associated with both HNF1A G319S (odds ratio (OR) 4.85, 95% CI 2.45, 9.58) and HTGW (OR 4.96, 95% CI 2.49, 9.88). When the HNF1A mutation and HTGW were present in combination, the OR for type 2 diabetes was markedly increased (OR 43.2, 95% CI 12.4, 150). In women only, both GNB3 825C>T and FABP2 A54T genotypes were significantly associated with HTGW (OR 2.02, 95% CI 1.01, 4.05 and OR 1.95, 95% CI 1.01, 3.74, respectively).

Conclusions:

HTGW is prevalent in Oji-Cree, especially in men. The ORs for type 2 diabetes were similar (∼5-fold) for subjects with either the presence of HTGW or the private HNF1A G319S mutation. These two independent risk factors acted synergistically to confer an even greater increased risk of type 2 diabetes.

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Acknowledgements

We thank Matthew Ban for his assistance in preparing the databases for analysis. We also gratefully acknowledge the chief, council and community members of Sandy Lake First Nation and the Sandy Lake community surveyors (Louisa Kakegamic, Tina Noon, Madeline Kakegamic, Elda Anishinabie, Annette Rae, Connie Kakegamic, and Mary Mamakeesick), whose partnership and co-operation was essential in the design and implementation of this project. RAH holds a Canada Research Chair (Tier I) and is a Career Investigator of the Heart and Stroke Foundation of Ontario. RLP is supported by a Natural Sciences and Engineering Research Council of Canada Graduate Scholarship and the Canadian Institute of Health Research Strategic Training Program in Vascular Research. AJGH was supported through a Canadian Diabetes Scholarship and a University of Toronto Banting and Best Diabetes Centre New Investigator Award. SBH is a Career Scientist of the Ontario Ministry of Health.

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Authors and Affiliations

  1. Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute and University of Western Ontario, London, Ontario, Canada

    R L Pollex & R A Hegele

  2. Department of Medicine, University of Toronto and Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada

    A J G Hanley & B Zinman

  3. Centre for Studies in Family Medicine, University of Western Ontario, London, Ontario, Canada

    S B Harris

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  1. R L Pollex
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  2. A J G Hanley
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  3. B Zinman
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  4. S B Harris
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  5. R A Hegele
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Correspondence to R A Hegele.

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Pollex, R., Hanley, A., Zinman, B. et al. Clinical and genetic associations with hypertriglyceridemic waist in a Canadian aboriginal population. Int J Obes 30, 484–491 (2006). https://doi.org/10.1038/sj.ijo.0803152

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