L. Bathum et al., Evidence for a substantial genetic influence on biochemical liver functiontests: Results from a population-based Danish twin study, CLIN CHEM, 47(1), 2001, pp. 81-87
Background: Biochemical liver function tests are widely used in the clinic
and are some of the most frequently used tests in screening for diseases in
older age groups. The aim of the present study was to estimate the relativ
e importance of genetic and environmental factors to variations in these te
sts among the elderly.
Methods: We conducted a survey among Danish twins, 73-102 years of age, ide
ntified in the population-based Danish Twin Registry. Among the 2749 indivi
duals in the study population, an interview was conducted with 79%. From th
ese, a blood sample was collected from 290 same-sex twin pairs, total of 58
0 subjects, within a 6-month period and analyzed for alanine aminotransfera
se (ALT), lactate dehydrogenase (LDH), gamma -glutamyltransferase (GGT), bi
lirubin, and albumin. The interview included questions about alcohol consum
ption and body mass index (BMI; self-calculated height and weight), Heritab
ility (proportion of the population variance attributable to genetic variat
ion) was estimated using structural-equation analyses before and after corr
ection for alcohol consumption and BMI.
Results: Structural-equation analyses revealed a substantial heritability (
35-61%) for the four biochemical liver function tests: ALT, GGT, LDH, and b
ilirubin. The remaining variation could lie attributed to individuals' nonf
amilial environments. Adjustment for alcohol consumption and BMI had no inf
luence on the heritability for ALT, GGT, LDH, and bilirubin. For albumin, t
wo models fit equally well before adjustment for alcohol and BMI: a model i
ncluding additive genetic and nonshared environmental factors (AE), and a m
odel including shared and nonshared environmental factors (CE). After adjus
tment, the model including shared and nonshared environment was clearly the
best fitting model.
Conclusions: For bdth males and females, the effect of genetic factors on t
he biochemical liver function tests ALT, GGT, LDH, and bilirubin is substan
tial and accounts for one-third to two-thirds of the:variation among indivi
duals 73-102 years of age. The heritability is equal for males and females
and does not change notably after controlling for alcohol consumption and B
MI. For albumin, no major impact of genetic factors was found independent o
f BMI and alcohol consumption. An understanding of the genetic mechanisms u
nderlying biochemical liver function tests among the very old may be of val
ue in the interpretation of these tests in this age group. (C) 2001 America
n Association for Clinical Chemistry.