A Longitudinal Genetic Study of Uric Acid and Liver Enzymes in Adolescent Twins

Abstract

Biochemical traits such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and uric acid are associated with obesity, and with risk of cardiovascular disease, metabolic syndrome and diabetes. Each is subject to genetic influences, but little is known about changes in genetic and environmental influences on these traits over time. We investigated the contribution of genetic and environmental influences to variation in these biochemical traits in adolescent twins and their nontwin siblings from 965 twin families. Twins were studied at ages 12, 14 and 16 years. Multivariate genetic models that included effects of age and sex were fitted to determine whether the same or different genetic or environmental factors influence each trait at different ages. Results showed that the genetic factors influencing AST, ALT, GGT and uric acid change over time during adolescence, and that the magnitude of these effects differs between males and females. The nonshared environment effects were generally time specific. There are developmental changes in genes affecting these traits during adolescence.

Family-based mitochondrial association study of traits related to type 2 diabetes and the metabolic syndrome in adolescents

“…There were no strong associations across age groups; however, this is not inconsistent with previous reports, which have suggested that different genetic factors may act upon these phenotypes at different times [25,35]. The increased number of large test statistics relative to the expected distribution for the association with triacylglycerol suggests that common mitochondrial variants may influence this trait in early adolescence.…”

“…The heritability estimates for each trait in our sample are high (Table 4), due to the heritability being estimated under an AE model, and there are strong phenotypic correlation across the three measurement time points [25,35,39]. Table 5 shows the most significant associations for each trait in the 12, 14 and 16 year age groups.…”

“…Height and BMI were also tested for association. Further information regarding the measurement of these variables have been described [25,35]. Participants were not instructed to fast before measurements were taken.…”

“…In addition, the concentration of uric acid, ferritin and a number of liver enzymes (γ-glutamyltransferase [GGT] and alanine aminotransferase [ALT]) that are risk factors for obesity, cardiovascular disease, diabetes and the metabolic syndrome were examined. Uric acid has been shown to be associated with the metabolic syndrome [24], while serum GGT and ALT, which have been shown to be correlated [25], have been associated with cardiovascular disease [26,27], hypertension and diabetes [27,28]. The sample was also measured for weight and height, and hence BMI.…”

Genetic factors contribute to variation in serum alanine aminotransferase activity independent of obesity and alcohol: A study in monozygotic and dizygotic twins

“…The heritability of liver function tests has previously been estimated in two twin studies [42,43]. Bathum et al investigated 290 pairs of elderly (age range 73-102 years) Danish same sex twins and found 35-61% heritability for S-ALT, S-GGT, serum bilirubin, serum albumin and serum lactate dehydrogenase [42].…”