Association of the alcohol dehydrogenase gene polymorphism rs1789891 with gray matter brain volume, alcohol consumption, alcohol craving and relapse risk
Alcohol metabolizing enzymes, such as the alcohol dehydrogenases and the aldehyde dehydrogenases, regulate the levels of acetaldehyde in the blood and play an important role in the development and maintenance of alcohol addiction. Recent genome‐wide systematic searches found associations between a s...
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| Veröffentlicht in: | Addiction biology 2019-01, Vol.24 (1), p.110-120 |
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| creator | Bach, Patrick Zois, Evangelos Vollstädt‐Klein, Sabine Kirsch, Martina Hoffmann, Sabine Jorde, Anne Frank, Josef Charlet, Katrin Treutlein, Jens Beck, Anne Heinz, Andreas Walter, Henrik Rietschel, Marcella Kiefer, Falk |
| description | Alcohol metabolizing enzymes, such as the alcohol dehydrogenases and the aldehyde dehydrogenases, regulate the levels of acetaldehyde in the blood and play an important role in the development and maintenance of alcohol addiction. Recent genome‐wide systematic searches found associations between a single nucleotide polymorphism (rs1789891, risk allele: A, protective allele: C) in the alcohol dehydrogenase gene cluster and the risk of alcohol dependence. The current study investigated the effect of this single nucleotide polymorphism on alcohol consumption, craving for alcohol, relapse risk and brain gray matter volume. Alcohol‐dependent patients (n = 74) and controls (n = 43) were screened, genotyped and underwent magnetic resonance imaging scanning, and relapse data were collected during 3 months following the experiment. Alcohol‐dependent A allele carriers reported increased alcohol craving and higher alcohol consumption compared with the group of alcohol‐dependent individuals homozygous for the C allele, which displayed craving values similar to the control group. Further, follow‐up data indicated that A allele carriers relapsed earlier to heavy drinking compared with individuals with two C alleles. Analyses of gray matter volume indicated a significant genotype difference in the patient group: individuals with two C alleles had reduced gray matter volume in the left and right superior, middle and inferior temporal gyri.
Findings of the current study further support the relevance of genetic variants in alcohol metabolizing enzymes to addictive behavior, brain tissue volume and relapse risk. Genotype‐dependent differences in acetaldehyde formation, implicated by earlier studies, might be the biological substrate of the genotype differences.
This study presents initial evidence that a genetic polymorphism in the alcohol dehydrogenase gene cluster (rs1789891), which was associated with alcohol dependence risk before, is associated with increased alcohol cue‐induced craving, higher alcohol consumption, gray matter volume loss in bilateral temporal gyri and higher relapse risk in alcohol dependent patients. |
| doi_str_mv | 10.1111/adb.12571 |
| format | Article |
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Findings of the current study further support the relevance of genetic variants in alcohol metabolizing enzymes to addictive behavior, brain tissue volume and relapse risk. Genotype‐dependent differences in acetaldehyde formation, implicated by earlier studies, might be the biological substrate of the genotype differences.
This study presents initial evidence that a genetic polymorphism in the alcohol dehydrogenase gene cluster (rs1789891), which was associated with alcohol dependence risk before, is associated with increased alcohol cue‐induced craving, higher alcohol consumption, gray matter volume loss in bilateral temporal gyri and higher relapse risk in alcohol dependent patients.</description><identifier>ISSN: 1355-6215</identifier><identifier>EISSN: 1369-1600</identifier><identifier>DOI: 10.1111/adb.12571</identifier><identifier>PMID: 29058369</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Acetaldehyde ; Addictions ; Addictive behaviors ; ADH gene polymorphism ; Adult ; Alcohol ; Alcohol dehydrogenase ; Alcohol Dehydrogenase - genetics ; Alcohol Drinking - genetics ; Alcohol use ; alcoholism ; Alcoholism - genetics ; Alleles ; Brain - diagnostic imaging ; Brain - pathology ; Craving ; Dehydrogenases ; Drinking behavior ; Drug addiction ; Drug dependence ; Enzymes ; Female ; Gene polymorphism ; Genetic diversity ; Genomes ; Genotype & phenotype ; Gray Matter - diagnostic imaging ; Gray Matter - pathology ; gray matter volume ; Humans ; Magnetic resonance imaging ; Male ; Middle Aged ; MRI ; Neuroimaging ; Organ Size - genetics ; Polymorphism ; Polymorphism, Single Nucleotide ; Proportional Hazards Models ; Recurrence ; relapse ; rs1789891 ; Single-nucleotide polymorphism ; Substantia grisea ; Temporal Lobe - diagnostic imaging ; Temporal Lobe - pathology</subject><ispartof>Addiction biology, 2019-01, Vol.24 (1), p.110-120</ispartof><rights>2017 Society for the Study of Addiction</rights><rights>2017 Society for the Study of Addiction.</rights><rights>2019 Society for the Study of Addiction</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3881-e514b6e839385f241df0dab8d2dae1f618ba3d5a8b9f63b7acc093ddfb111fa93</citedby><cites>FETCH-LOGICAL-c3881-e514b6e839385f241df0dab8d2dae1f618ba3d5a8b9f63b7acc093ddfb111fa93</cites><orcidid>0000-0001-5962-019X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fadb.12571$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fadb.12571$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29058369$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bach, Patrick</creatorcontrib><creatorcontrib>Zois, Evangelos</creatorcontrib><creatorcontrib>Vollstädt‐Klein, Sabine</creatorcontrib><creatorcontrib>Kirsch, Martina</creatorcontrib><creatorcontrib>Hoffmann, Sabine</creatorcontrib><creatorcontrib>Jorde, Anne</creatorcontrib><creatorcontrib>Frank, Josef</creatorcontrib><creatorcontrib>Charlet, Katrin</creatorcontrib><creatorcontrib>Treutlein, Jens</creatorcontrib><creatorcontrib>Beck, Anne</creatorcontrib><creatorcontrib>Heinz, Andreas</creatorcontrib><creatorcontrib>Walter, Henrik</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Kiefer, Falk</creatorcontrib><title>Association of the alcohol dehydrogenase gene polymorphism rs1789891 with gray matter brain volume, alcohol consumption, alcohol craving and relapse risk</title><title>Addiction biology</title><addtitle>Addict Biol</addtitle><description>Alcohol metabolizing enzymes, such as the alcohol dehydrogenases and the aldehyde dehydrogenases, regulate the levels of acetaldehyde in the blood and play an important role in the development and maintenance of alcohol addiction. Recent genome‐wide systematic searches found associations between a single nucleotide polymorphism (rs1789891, risk allele: A, protective allele: C) in the alcohol dehydrogenase gene cluster and the risk of alcohol dependence. The current study investigated the effect of this single nucleotide polymorphism on alcohol consumption, craving for alcohol, relapse risk and brain gray matter volume. Alcohol‐dependent patients (n = 74) and controls (n = 43) were screened, genotyped and underwent magnetic resonance imaging scanning, and relapse data were collected during 3 months following the experiment. Alcohol‐dependent A allele carriers reported increased alcohol craving and higher alcohol consumption compared with the group of alcohol‐dependent individuals homozygous for the C allele, which displayed craving values similar to the control group. Further, follow‐up data indicated that A allele carriers relapsed earlier to heavy drinking compared with individuals with two C alleles. Analyses of gray matter volume indicated a significant genotype difference in the patient group: individuals with two C alleles had reduced gray matter volume in the left and right superior, middle and inferior temporal gyri.
Findings of the current study further support the relevance of genetic variants in alcohol metabolizing enzymes to addictive behavior, brain tissue volume and relapse risk. Genotype‐dependent differences in acetaldehyde formation, implicated by earlier studies, might be the biological substrate of the genotype differences.
This study presents initial evidence that a genetic polymorphism in the alcohol dehydrogenase gene cluster (rs1789891), which was associated with alcohol dependence risk before, is associated with increased alcohol cue‐induced craving, higher alcohol consumption, gray matter volume loss in bilateral temporal gyri and higher relapse risk in alcohol dependent patients.</description><subject>Acetaldehyde</subject><subject>Addictions</subject><subject>Addictive behaviors</subject><subject>ADH gene polymorphism</subject><subject>Adult</subject><subject>Alcohol</subject><subject>Alcohol dehydrogenase</subject><subject>Alcohol Dehydrogenase - genetics</subject><subject>Alcohol Drinking - genetics</subject><subject>Alcohol use</subject><subject>alcoholism</subject><subject>Alcoholism - genetics</subject><subject>Alleles</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - pathology</subject><subject>Craving</subject><subject>Dehydrogenases</subject><subject>Drinking behavior</subject><subject>Drug addiction</subject><subject>Drug dependence</subject><subject>Enzymes</subject><subject>Female</subject><subject>Gene polymorphism</subject><subject>Genetic diversity</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Gray Matter - diagnostic imaging</subject><subject>Gray Matter - pathology</subject><subject>gray matter volume</subject><subject>Humans</subject><subject>Magnetic resonance imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>MRI</subject><subject>Neuroimaging</subject><subject>Organ Size - genetics</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proportional Hazards Models</subject><subject>Recurrence</subject><subject>relapse</subject><subject>rs1789891</subject><subject>Single-nucleotide polymorphism</subject><subject>Substantia grisea</subject><subject>Temporal Lobe - diagnostic imaging</subject><subject>Temporal Lobe - pathology</subject><issn>1355-6215</issn><issn>1369-1600</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhi0EoqVw4AWQJS4gkdaO14l9XAqUSpW4wNkax_bGxYmDnbTKo_Rt8bKlQkidy4ysT99Y8yP0mpJTWuoMjD6lNW_pE3RMWSMr2hDydD9zXjU15UfoRc7XhNC65ew5Oqol4aKAx-hum3PsPMw-jjg6PPcWQ-hiHwM2tl9Nijs7Qra4NIunGNYhpqn3ecAp01ZIISm-9XOPdwlWPMA824R1Aj_imxiWwX54EHZxzMsw7Xf985jgxo87DKPByQaYyq7k88-X6JmDkO2r-36Cfnz5_P38a3X17eLyfHtVdUwIWllON7qxgkkmuKs31DhiQAtTG7DUNVRoYIaD0NI1TLfQdUQyY5wul3Mg2Ql6d_BOKf5abJ7V4HNnQ4DRxiUrKvlmU9eCioK-_Q-9jksay-9UObJkvG1ZW6j3B6pLMedknZqSHyCtihK1z0uVvNSfvAr75t646MGaB_JvQAU4OwC3Ptj1cZPafvp4UP4GH_uhQw</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Bach, Patrick</creator><creator>Zois, Evangelos</creator><creator>Vollstädt‐Klein, Sabine</creator><creator>Kirsch, Martina</creator><creator>Hoffmann, Sabine</creator><creator>Jorde, Anne</creator><creator>Frank, Josef</creator><creator>Charlet, Katrin</creator><creator>Treutlein, Jens</creator><creator>Beck, Anne</creator><creator>Heinz, Andreas</creator><creator>Walter, Henrik</creator><creator>Rietschel, Marcella</creator><creator>Kiefer, Falk</creator><general>John Wiley & Sons, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5962-019X</orcidid></search><sort><creationdate>201901</creationdate><title>Association of the alcohol dehydrogenase gene polymorphism rs1789891 with gray matter brain volume, alcohol consumption, alcohol craving and relapse risk</title><author>Bach, Patrick ; Zois, Evangelos ; Vollstädt‐Klein, Sabine ; Kirsch, Martina ; Hoffmann, Sabine ; Jorde, Anne ; Frank, Josef ; Charlet, Katrin ; Treutlein, Jens ; Beck, Anne ; Heinz, Andreas ; Walter, Henrik ; Rietschel, Marcella ; Kiefer, Falk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3881-e514b6e839385f241df0dab8d2dae1f618ba3d5a8b9f63b7acc093ddfb111fa93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acetaldehyde</topic><topic>Addictions</topic><topic>Addictive behaviors</topic><topic>ADH gene polymorphism</topic><topic>Adult</topic><topic>Alcohol</topic><topic>Alcohol dehydrogenase</topic><topic>Alcohol Dehydrogenase - genetics</topic><topic>Alcohol Drinking - genetics</topic><topic>Alcohol use</topic><topic>alcoholism</topic><topic>Alcoholism - genetics</topic><topic>Alleles</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - pathology</topic><topic>Craving</topic><topic>Dehydrogenases</topic><topic>Drinking behavior</topic><topic>Drug addiction</topic><topic>Drug dependence</topic><topic>Enzymes</topic><topic>Female</topic><topic>Gene polymorphism</topic><topic>Genetic diversity</topic><topic>Genomes</topic><topic>Genotype & phenotype</topic><topic>Gray Matter - diagnostic imaging</topic><topic>Gray Matter - pathology</topic><topic>gray matter volume</topic><topic>Humans</topic><topic>Magnetic resonance imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>MRI</topic><topic>Neuroimaging</topic><topic>Organ Size - genetics</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proportional Hazards Models</topic><topic>Recurrence</topic><topic>relapse</topic><topic>rs1789891</topic><topic>Single-nucleotide polymorphism</topic><topic>Substantia grisea</topic><topic>Temporal Lobe - diagnostic imaging</topic><topic>Temporal Lobe - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bach, Patrick</creatorcontrib><creatorcontrib>Zois, Evangelos</creatorcontrib><creatorcontrib>Vollstädt‐Klein, Sabine</creatorcontrib><creatorcontrib>Kirsch, Martina</creatorcontrib><creatorcontrib>Hoffmann, Sabine</creatorcontrib><creatorcontrib>Jorde, Anne</creatorcontrib><creatorcontrib>Frank, Josef</creatorcontrib><creatorcontrib>Charlet, Katrin</creatorcontrib><creatorcontrib>Treutlein, Jens</creatorcontrib><creatorcontrib>Beck, Anne</creatorcontrib><creatorcontrib>Heinz, Andreas</creatorcontrib><creatorcontrib>Walter, Henrik</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Kiefer, Falk</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Addiction biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bach, Patrick</au><au>Zois, Evangelos</au><au>Vollstädt‐Klein, Sabine</au><au>Kirsch, Martina</au><au>Hoffmann, Sabine</au><au>Jorde, Anne</au><au>Frank, Josef</au><au>Charlet, Katrin</au><au>Treutlein, Jens</au><au>Beck, Anne</au><au>Heinz, Andreas</au><au>Walter, Henrik</au><au>Rietschel, Marcella</au><au>Kiefer, Falk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of the alcohol dehydrogenase gene polymorphism rs1789891 with gray matter brain volume, alcohol consumption, alcohol craving and relapse risk</atitle><jtitle>Addiction biology</jtitle><addtitle>Addict Biol</addtitle><date>2019-01</date><risdate>2019</risdate><volume>24</volume><issue>1</issue><spage>110</spage><epage>120</epage><pages>110-120</pages><issn>1355-6215</issn><eissn>1369-1600</eissn><abstract>Alcohol metabolizing enzymes, such as the alcohol dehydrogenases and the aldehyde dehydrogenases, regulate the levels of acetaldehyde in the blood and play an important role in the development and maintenance of alcohol addiction. Recent genome‐wide systematic searches found associations between a single nucleotide polymorphism (rs1789891, risk allele: A, protective allele: C) in the alcohol dehydrogenase gene cluster and the risk of alcohol dependence. The current study investigated the effect of this single nucleotide polymorphism on alcohol consumption, craving for alcohol, relapse risk and brain gray matter volume. Alcohol‐dependent patients (n = 74) and controls (n = 43) were screened, genotyped and underwent magnetic resonance imaging scanning, and relapse data were collected during 3 months following the experiment. Alcohol‐dependent A allele carriers reported increased alcohol craving and higher alcohol consumption compared with the group of alcohol‐dependent individuals homozygous for the C allele, which displayed craving values similar to the control group. Further, follow‐up data indicated that A allele carriers relapsed earlier to heavy drinking compared with individuals with two C alleles. Analyses of gray matter volume indicated a significant genotype difference in the patient group: individuals with two C alleles had reduced gray matter volume in the left and right superior, middle and inferior temporal gyri.
Findings of the current study further support the relevance of genetic variants in alcohol metabolizing enzymes to addictive behavior, brain tissue volume and relapse risk. Genotype‐dependent differences in acetaldehyde formation, implicated by earlier studies, might be the biological substrate of the genotype differences.
This study presents initial evidence that a genetic polymorphism in the alcohol dehydrogenase gene cluster (rs1789891), which was associated with alcohol dependence risk before, is associated with increased alcohol cue‐induced craving, higher alcohol consumption, gray matter volume loss in bilateral temporal gyri and higher relapse risk in alcohol dependent patients.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>29058369</pmid><doi>10.1111/adb.12571</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5962-019X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acetaldehyde Addictions Addictive behaviors ADH gene polymorphism Adult Alcohol Alcohol dehydrogenase Alcohol Dehydrogenase - genetics Alcohol Drinking - genetics Alcohol use alcoholism Alcoholism - genetics Alleles Brain - diagnostic imaging Brain - pathology Craving Dehydrogenases Drinking behavior Drug addiction Drug dependence Enzymes Female Gene polymorphism Genetic diversity Genomes Genotype & phenotype Gray Matter - diagnostic imaging Gray Matter - pathology gray matter volume Humans Magnetic resonance imaging Male Middle Aged MRI Neuroimaging Organ Size - genetics Polymorphism Polymorphism, Single Nucleotide Proportional Hazards Models Recurrence relapse rs1789891 Single-nucleotide polymorphism Substantia grisea Temporal Lobe - diagnostic imaging Temporal Lobe - pathology |
| title | Association of the alcohol dehydrogenase gene polymorphism rs1789891 with gray matter brain volume, alcohol consumption, alcohol craving and relapse risk |
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