Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study.
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 relative importance of genetic and environmental factors to variations in these tests among the elderly.


METHODS
We conducted a survey among Danish twins, 73-102 years of age, identified in the population-based Danish Twin Registry. Among the 2749 individuals in the study population, an interview was conducted with 79%. From these, a blood sample was collected from 290 same-sex twin pairs, total of 580 subjects, within a 6-month period and analyzed for alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and albumin. The interview included questions about alcohol consumption and body mass index (BMI; self-calculated height and weight). Heritability (proportion of the population variance attributable to genetic variation) was estimated using structural-equation analyses before and after correction 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 bilirubin. The remaining variation could be attributed to individuals' nonfamilial environments. Adjustment for alcohol consumption and BMI had no influence on the heritability for ALT, GGT, LDH, and bilirubin. For albumin, two models fit equally well before adjustment for alcohol and BMI: a model including additive genetic and nonshared environmental factors (AE), and a model including shared and nonshared environmental factors (CE). After adjustment, the model including shared and nonshared environment was clearly the best fitting model.


CONCLUSIONS
For both males and females, the effect of genetic factors on the biochemical liver function tests ALT, GGT, LDH, and bilirubin is substantial and accounts for one-third to two-thirds of the variation among individuals 73-102 years of age. The heritability is equal for males and females and does not change notably after controlling for alcohol consumption and BMI. For albumin, no major impact of genetic factors was found independent of BMI and alcohol consumption. An understanding of the genetic mechanisms underlying biochemical liver function tests among the very old may be of value in the interpretation of these tests in this age group.
Bathum
L
L
Department of Clinical Biochemistry, Odense University Hospital, DK-5000 Odense C, Denmark. Lise.Bathum@ouh.fyns-amt.dk
Petersen
H C
HC
Rosholm
J U
JU
Hyltoft Petersen
P
P
Vaupel
J
J
Christensen
K
K
D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000418:Albumins / Q000032:analysis; D000428:Alcohol Drinking; D001663:Bilirubin / Q000032:analysis; D015992:Body Mass Index; D003627:Data Interpretation, Statistical; D003718:Denmark; D004777:Environment; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007407:Interviews as Topic; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D018433:Twin Studies as Topic; D005723:gamma-Glutamyltransferase / Q000097:blood
D000418:Albumins; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D001663:Bilirubin