Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30589442
TITLE
Biomarker and genomic risk factors for liver function test abnormality in hazardous drinkers.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Alcohol dependence and long-term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests, particularly gamma-glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical liver function tests could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers.
METHODS NlmCategory: METHODS
Alcohol dependence and long-term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests, particularly gamma-glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical liver function tests could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers. Data from participants in twin and twin-family studies on alcohol use and dependence were used to identify 1003 people who had reported excessive alcohol intake (28 drinks or more per week). 962 of these provided blood for biochemical tests at the same time. Body mass index (BMI) and biomarkers of metabolic syndrome, inflammation, and iron stores, were used in logistic regression with abnormality in serum GGT, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) as outcomes. We conducted genome-wide association analyses for GGT, ALT and AST separately in the group reporting excessive alcohol intake (N=951) and a low-intake group reporting 14 drinks or fewer per week (N=8716), and compared results.
RESULTS NlmCategory: RESULTS
Alcohol dependence and long-term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests, particularly gamma-glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical liver function tests could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers. Data from participants in twin and twin-family studies on alcohol use and dependence were used to identify 1003 people who had reported excessive alcohol intake (28 drinks or more per week). 962 of these provided blood for biochemical tests at the same time. Body mass index (BMI) and biomarkers of metabolic syndrome, inflammation, and iron stores, were used in logistic regression with abnormality in serum GGT, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) as outcomes. We conducted genome-wide association analyses for GGT, ALT and AST separately in the group reporting excessive alcohol intake (N=951) and a low-intake group reporting 14 drinks or fewer per week (N=8716), and compared results. Abnormal GGT and ALT among excessive drinkers were associated with higher BMI, triglycerides, insulin, uric acid, C-reactive protein, ferritin and transferrin saturation; and with lower HDL cholesterol. Abnormal AST was associated with triglycerides, ferritin and transferrin saturation. ALT was significantly associated with variants at reported genetic loci for alcoholic liver disease (PNPLA3, rs738409 p = 0.0076; TM6SF2, rs10401969 p = 0.0076; HSD17B13, rs10433879 p = 0.0024).
CONCLUSIONS NlmCategory: CONCLUSIONS
Alcohol dependence and long-term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests, particularly gamma-glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical liver function tests could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers. Data from participants in twin and twin-family studies on alcohol use and dependence were used to identify 1003 people who had reported excessive alcohol intake (28 drinks or more per week). 962 of these provided blood for biochemical tests at the same time. Body mass index (BMI) and biomarkers of metabolic syndrome, inflammation, and iron stores, were used in logistic regression with abnormality in serum GGT, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) as outcomes. We conducted genome-wide association analyses for GGT, ALT and AST separately in the group reporting excessive alcohol intake (N=951) and a low-intake group reporting 14 drinks or fewer per week (N=8716), and compared results. Abnormal GGT and ALT among excessive drinkers were associated with higher BMI, triglycerides, insulin, uric acid, C-reactive protein, ferritin and transferrin saturation; and with lower HDL cholesterol. Abnormal AST was associated with triglycerides, ferritin and transferrin saturation. ALT was significantly associated with variants at reported genetic loci for alcoholic liver disease (PNPLA3, rs738409 p = 0.0076; TM6SF2, rs10401969 p = 0.0076; HSD17B13, rs10433879 p = 0.0024). Known risk factors for alcoholic cirrhosis including obesity and markers of metabolic syndrome, iron overload, and inflammation are associated with liver enzyme abnormality in excessive drinkers. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
DATE PUBLISHED
2018 Dec 27
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2018/12/28 06:00
pubmed 2018/12/28 06:00
medline 2018/12/28 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Whitfield JB Whitfield John B JB QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, 4006, Queensland, Australia.
Zhu G Zhu Gu G QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, 4006, Queensland, Australia.
Madden PA Madden Pamela Af PA Department of Psychiatry, Washington University School of Medicine, St Louis, MO, 63110, USA.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, St Lucia, 4072, Queensland, Australia.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, St Louis, MO, 63110, USA.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, 4006, Queensland, Australia.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Alcoholism, clinical and experimental research
ISOABBREVIATION: Alcohol. Clin. Exp. Res.
YEAR: 2018
MONTH: Dec
DAY: 27
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1530-0277
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Alcohol Clin Exp Res
COUNTRY: England
ISSNLINKING: 0145-6008
NLMUNIQUEID: 7707242
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
ALT
AST
GGT
Alcohol
cirrhosis
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's