Genetic covariation between serum gamma-glutamyltransferase activity and cardiovascular risk factors.
BACKGROUND
Several studies have shown that variation in serum gamma-glutamyltransferase (GGT) in the population is associated with risk of death or development of cardiovascular disease, type 2 diabetes, stroke, or hypertension. This association is only partly explained by associations between GGT and recognized risk factors. Our aim was to estimate the relative importance of genetic and environmental sources of variation in GGT as well as genetic and environmental sources of covariation between GGT and other liver enzymes and markers of cardiovascular risk in adult twin pairs.


METHODS
We recruited 1134 men and 2241 women through the Australian Twin Registry. Data were collected through mailed questionnaires, telephone interviews, and by analysis of blood samples. Sources of variation in GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and of covariation between GGT and cardiovascular risk factors were assessed by maximum-likelihood model-fitting.


RESULTS
Serum GGT, ALT, and AST were affected by additive genetic and nonshared environmental factors, with heritabilities estimated at 0.52, 0.48, and 0.32, respectively. One-half of the genetic variance in GGT was shared with ALT, AST, or both. There were highly significant correlations between GGT and body mass index; serum lipids, lipoproteins, glucose, and insulin; and blood pressure. These correlations were more attributable to genes that affect both GGT and known cardiovascular risk factors than to environmental factors.


CONCLUSIONS
Variation in serum enzymes that reflect liver function showed significant genetic effects, and there was evidence that both genetic and environmental factors that affect these enzymes can also affect cardiovascular risk.
Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia. John.Whitfield@mail.cs.nsw.gov.au
John B
JB
Whitfield
Gu
G
Zhu
John E
JE
Nestler
Andrew C
AC
Heath
Nicholas G
NG
Martin
D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000235:genetics*; D003627:Data Interpretation, Statistical; D004777:Environment; D005260:Female; D006801:Humans; D008297:Male; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000097:blood*
D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase