Epidemiology and genetic epidemiology of the liver function test proteins.
BACKGROUND
The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI).


OBJECTIVE
To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins--including alanine amino transaminase (ALT), Albumin, gamma glutamyl transpeptidase (GGT), total bilirubin, total protein, total globulin, aspartate transaminase (AST), and alkaline phosphotase (ALP)--using the classical twin model.


METHODS
Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry. We measured the expression levels of major proteins associated with the LFT, calculated BMI from measured weight and height and questionnaires were completed for alcohol consumption by the twins. The relative contribution of genetic and environmental factors to variation in the LFT proteins was assessed and quantified using a variance components model fitting approach.


RESULTS
Our results show that (1) variation in all the LFTs has a significant heritable basis (h(2) ranging from 20% to 77%); (2) other than GGT, the LFTs are all affected to some extent by common environmental factors (c(2) ranging from 24% to 54%); and (3) a small but significant proportion of the variation in the LFTs was due to confounding effects of age, sex, BMI, and alcohol use.


CONCLUSIONS
Variation in the LFT proteins is under significant genetic and common environmental control although sex, alcohol use, age and BMI also contribute significantly to inter-individual variation in the LFT proteins. Understanding the underlying genetic contribution of liver function tests may help the interpretation of their results and explain wide variation among individuals.
Rahmioglu
Nilufer
N
Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Andrew
Toby
T
Cherkas
Lynn
L
Surdulescu
Gabriela
G
Swaminathan
Ramasamyiyer
R
Spector
Tim
T
Ahmadi
Kourosh R
KR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000428:Alcohol Drinking; D015992:Body Mass Index; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D017720:Molecular Epidemiology; D011506:Proteins / Q000378:metabolism*; D012044:Regression Analysis; D012727:Sex Characteristics; D014427:Twins
D011506:Proteins