|
|
| PMID |
|
|
| 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 |
|
|
| 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 |
|
|
|
