Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins

Abstract

BackgroundThe 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).AimsTo 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.MethodsBlood 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.ResultsOur results show that (1) variation in all the LFTs has a significant heritable basis (h2 ranging from 20% to 77%); (2) other than GGT, the LFTs are all affected to some extent by common environmental factors (c2 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.ConclusionsVariation 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.

Genetic variants in COL13A1, ADIPOQ and SAMM50 , in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population

“…Twin studies suggest that transaminase levels have a genetic heritability irrespective of anthropometric features and environmental factors (Bathum et al, 2001; Rahmioglu et al, 2009), which means that certain genes may regulate liver enzyme levels. Studies of genetic regions like PNPLA3 , SAMM50 and PARVB support this idea, since variants in these genes have been associated with NAFLD and elevated ALT and AST levels (Flores et al, 2016; Kitamoto et al, 2013; Ravi Kanth et al, 2014).…”

Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead

“…Liver enzymes γGT, ALT and AST are used as biomarkers to test liver function and hepatic integrity (Rahmioglu et al, 2009). Damage to the hepatocyte membrane will cause the release of many of these enzymes into the circulating blood.…”

The Effect of Vanadium Citrate on the Metabolism of Proteins in Rats’ Blood with Alloxan-Induced Diabetes Mellitus

“…Як свідчать дані літератури, за умов діабету як І, так і ІІ типу активність ЛФ значно підвищується, проте за ЦД ІІ типу активність ензиму є вищою, ніж за ЦД І типу, чим пояснюється печінкова дисфункція за ЦД ІІ [12].…”

“…Зростання АсАТ і АлАТ сигналізує про розвиток ЦД. Активності печі-нкових ензимів γ-глютамілтрансферази, АлАТ та АсАТ корелюють один з одним [16], мають загальні генетичні взаємозалежні зміни за патологічних ста-нів, в тому числі за діабету [12]. Можна припустити, що зв'язок між активністю AсАT і ризиком розвитку ЦД ІІ може бути опосередкований через вплив ін-ших ензимів печінки [8].…”