A null mutation in ANGPTL8 does not associate with either plasma glucose or type 2 diabetes in humans

作者：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^*

来源：BMC Endocrine Disorders, 2016, 16(1): 7.

DOI：10.1186/s12902-016-0088-8

• Betatrophin
• Angiopoietin-like 8
• rs145464906

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 similar to 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.

• 出版日期2016-1-28