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Genetic Covariation between Serum -Glutamyltransferase Activity and Cardiovascular Risk Factors

¹ Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia, and University of Sydney, Sydney NSW 2006, Australia.

² The Queensland Institute of Medical Research and the Joint Genetics Program, University of Queensland, Brisbane QLD 4029, Australia.

³ Division of Endocrinology, Medical College of Virginia, Richmond, VA 23398.

⁴ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108.

^aAddress correspondence to this author at: Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia. Fax 61-2-9515-7931; e-mail John.Whitfield{at}email.cs.nsw.gov.au.

Background: Several studies have shown that variation in serum -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.

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