Abstract

Background

Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.

Methods

We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45–74) living in the Boston metropolitan area.

Results

Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009), Stroop color naming score (P = 0.014) and Stroop color-word score (P = 0.022) compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032) and total cholesterol (P = 0.028) compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004), total cholesterol (P = 0.003) and glucose (P = 0.016) compared to CC subjects.

Conclusions

In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted.

Notes

Originally published in PLoS ONE 4(5): e5465 (2009). doi:10.1371/journal.pone.0005465

Supported by the National Institutes of Health, National Institute on Aging, Grant Number 5P01AG023394 and NIH/NHLBI grant number HL54776 and NIH/NIDDK DK075030 and contracts 53-K06-5-10 and 58-1950-9-001 from the U.S. Department of Agriculture Research Service. C. Smith is supported by T32 DK007651-19. M. Junyent is supported by the Fulbright-Spanish Ministry of Education and Science (reference 2007-1086). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Dr. Tucker is affiliated with Northeastern University at the time of deposit.

Keywords

apolioprotein C3 (APOC3), metabolism, diabetes, Hispanic

Subject Categories

Apolipoproteins, Cognition disorders, Metabolism - Disorders, Caribbean Americans

Disciplines

Nutritional and Metabolic Diseases

Publisher

Public Library of Science

Publication Date

5-8-2009

Restrictions

This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Rights Holder

Smith, et al.

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tucker table1.tif (453 kB)
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Table 2
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