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Updated: Apr 14, 2026

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
Functional characterization of two single nucleotide polymorphisms of acyl-coenzyme A:cholesterol acyltransferase 2
Xuelian He1, Koon-Yeow Leow2, Hongyuan Yang3
1Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore; Central Laboratory, Wuhan Children's Hospital, China.
Background:
Acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) plays a critical role in the formation of cholesteryl esters from cholesterol and fatty acids, and is a potential target for treating hypercholesterolemia. We recently reported the significant effects of two human ACAT2 gene polymorphisms, 41A>G (Glu(14)Gly, rs9658625) and 734C>T (Thr(254)Ile, rs2272296), on plasma lipid levels and coronary artery disease susceptibility in a case-control association study. In the present study, we evaluated the possible biological influence of the two polymorphism using two approaches.
Methods:
In the first approach, the functional impact of the two polymorphisms was predicted in-silico using available web-based software, and in the second approach, the varying functions of the two polymorphisms were characterized in in vitro experiments, using ACAT2-deficient AC-29 cells.
Results:
Our results show that the enzymatic activity of mutant Glu(14)Gly is approximately two times higher than wildtype, and that this increase is primarily due to the increased expression and/or stability of the mutant ACAT2 protein.
Conclusions:
These results suggest that the genetic variation at Glu(14)Gly is functionally important and may contribute to ACAT2 protein expression and stability.
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