Heritability of thromboxane A2 and prostaglandin E2 biosynthetic machinery in a Spanish population.
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.


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-A(2) and prostaglandin-E(2) 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.
H.S. Creu i S. Pau, S. Antonio M Claret 167, 08025-Barcelona, Spain. lvila@santpau.cat
Luis
L
Vila
Angel
A
Martinez-Perez
Mercedes
M
Camacho
Alfonso
A
Buil
Sonia
S
Alcolea
Nuria
N
Pujol-Moix
Marta
M
Soler
Rosa
R
Antón
Juan-Carlos
JC
Souto
Jordi
J
Fontcuberta
José-Manuel
JM
Soria
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001808:Blood Vessels / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004777:Environment; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010976:Platelet Count; D000071876:Prostaglandin-E Synthases; D013030:Spain; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000235:genetics / Q000378:metabolism; D014657:Vasculitis / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
D004798:Enzymes; D013928:Thromboxane A2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D013930:Thromboxane-A Synthase; D015232:Dinoprostone