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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.

Apolipoprotein C3 Polymorphisms, Cognitive Function and Diabetes in Caribbean Origin Hispanics