Alleles associated with lower levels of low density lipoprotein cholesterol (LDL-C) have recently been associated with an increased risk of type 2 diabetes (T2D), highlighting the complex relationship between LDL-C and diabetes. This observation begs the question whether LDL-C-raising alleles are associated with a decreased risk of T2D. This issue was recently addressed in a large familial hypercholesterolemia (FH) screening study, which reported a lower prevalence of self-reported diabetes in FH subjects than age-matched relatives without FH. To extend this observation, we tested the association of the FH with diabetes status and glycemia in a large Amish population enriched for the FH-associated APOB R3527Q variant that included 640 APOB R3527Q carriers and 4683 noncarriers. Each copy of the R3527Q T allele was associated with a 74.9 mg/dl increase in LDL-C. There was little difference in T2D prevalence between subjects with (5.2%) vs. without (4.5%) the R3527Q allele (p=0.23), nor was there any association with impaired fasting glucose, fasting glucose or insulin, or oral glucose tolerance (OGTT)-derived measures. Our data provide no evidence supporting an association between the APOB R3527Q variant with T2D or glycemia and highlight the asymmetry of the LDL-C-T2D relationship and/or the gene/variant-dependent specificity of the LDL-C-T2D association.
- Received February 10, 2017.
- Accepted April 14, 2017.
- © 2017 by the American Diabetes Association.