on October 22, 2009
Published online before print October 22, 2009, doi: 10.1161/ATVBAHA.109.193219
Submitted on June 16, 2009
Accepted on October 14, 2009
Heritability of Thromboxane A2 and Prostaglandin E2 Biosynthetic Machinery in a Spanish Population
Luis Vila *;
From the Laboratory of Angiology, Vascular Biology, and Inflammation (L.V., M.C., S.A., M.S., R.A.) and the Unit of Genomic of Complex Diseases (A.M.-P., A.B., J.-M.S.), Research Institute Hospital de la Santa Creu i Sant Pau, and the Department of Hematology (N.P.-M., J.-C.S., J.F.), Hospital Santa Creu i Sant Pau, Barcelona, Spain.
* To whom correspondence should be addressed. E-mail: lvila{at}santpau.cat.
Objective—Prostanoids play a critical role in clinical areas such as inflammation, thrombosis, immune response, and cancer. Although some studies suggest that there are genes that determine variability of some prostanoid-related phenotypes, the genetic influence on these traits has not been evaluated.
Methods and Results—The relative contributions of genetic and environmental influences to the prostanoid biosynthetic pathway-related phenotypes, cyclooxygenase isoenzymes, microsomal-PGE-synthase-1 and TxA-synthase expression, and thromboxane-A2 and prostaglandin-E2 production by stimulated whole blood, were assessed in a sample of 308 individuals in 15 extended families. The effects of measured covariates (such as sex, age, and smoking), genes, and environmental variables shared by members of a household were quantified. Heritabilities ranging from 0.406 to 0.634 for enzyme expression and from 0.283 to 0. 751 for prostanoid production were found.
Conclusions—These results demonstrate clearly the importance of genetic factors in determining variation in phenotypes that are components of the prostanoid biosynthetic pathways. The presence of such strong genetic effects suggest that it will be possible to localize previously unknown genes that influence quantitative variation in these phenotypes, some of which affect multiple aspects of cell biology, with important clinical implications.
Key words: atherosclerosis • gene expression • prostaglandins • thrombosis • thromboxanes • genomics