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- Title
A null mutation in does not ANGPTL8 associate with either plasma glucose or type 2 diabetes in humans.
- Authors
Clapham, Katharine R.; Chu, Audrey Y.; Wessel, Jennifer; Natarajan, Pradeep; Flannick, Jason; Rivas, Manuel A.; Sartori, Samantha; Mehran, Roxana; Baber, Usman; Fuster, Valentin; Scott, Robert A.; Rader, Daniel J.; Boehnke, Michael; McCarthy, Mark I.; Altshuler, David M.; Kathiresan, Sekar; Peloso, Gina M.
- Abstract
Background: Experiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis. However, subsequent experiments in model systems have challenged this proposed role. We sought to better understand the importance of ANGPTL8 in human glucose homeostasis by examining the association of a null mutation in ANGPTL8 with fasting glucose levels and risk for type 2 diabetes. Methods: A naturally-occurring null mutation in human ANGPTL8 (rs145464906; c.361C > T; p.Q121X) is carried by ~1 in 1000 individuals of European ancestry and is associated with higher levels of plasma high-density lipoprotein cholesterol, suggesting that this mutation has functional significance. We examined the association of p.Q121X with fasting glucose levels and risk for type 2 diabetes in up to 95,558 individuals (14,824 type 2 diabetics and 80,734 controls). Results: We found no significant association of p.Q121X with either fasting glucose or type 2 diabetes (p-value = 0.90 and 0.65, respectively). Given our sample sizes, we had >98 % power to detect at least a 0.23 mmol/L effect on plasma glucose and >95 % power to detect a 70 % increase in risk for type 2 diabetes. Conclusion: Disruption of ANGPTL8 function in humans does not seem to have a large effect on measures of glucose tolerance.
- Subjects
EUROPE; GENETICS of type 2 diabetes; GROWTH factors; RESEARCH methodology; GENETIC mutation; REGRESSION analysis; RESEARCH funding; PHENOTYPES; GENOTYPES
- Publication
BMC Endocrine Disorders, 2016, Vol 16, p1
- ISSN
1472-6823
- Publication type
Article
- DOI
10.1186/s12902-016-0088-8