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Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans
Introduction The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV...
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| Published in: | Alcoholism, clinical and experimental research clinical and experimental research, 2014-01, Vol.38 (1), p.51-59 |
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| creator | Marshall, Vanessa J. Ramchandani, Vijay A. Kalu, Nnenna Kwagyan, John Scott, Denise M. Ferguson, Clifford L. Taylor, Robert E. |
| description | Introduction
The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers.
Materials
The sample included eighty‐seven 21‐ to 35‐year‐old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates.
Results
Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p |
| doi_str_mv | 10.1111/acer.12212 |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3946927</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3186594201</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4862-d1950f9640306fba41395defae089b2d7deda02af14793e72697acd9d15fc0533</originalsourceid><addsrcrecordid>eNp9kV9v0zAUxS0EYmXwwgdAkXhDyri2888vSF0pY6gCVIH2aLnJ9eLhxMVOtvXb4y5rBS_45Vq-v3N8pEPIawpnNJ73qkZ_Rhmj7AmZ0ZxDCqwsn5IZ0CxPC4DqhLwI4QYAsqoonpMTxgXNWZbPyLC8VXZUg3F94nQytJhc9tqO2Ne4f5jb2rXOJh-x3TXeXWOvAibfnd11zm9bE7qQROkBW1rTmX6yW6sBQ2LiUntTqzg7fLiEl-SZVjbgq8d5Sn5-Wv5YfE5X3y4uF_NVWsecLG2oyEGLIgMOhd6ojHKRN6gVQiU2rCkbbBQwpWlWCo4lK0Sp6kY0NNc15Jyfkg-T73bcdNjU2A9eWbn1plN-J50y8t9Nb1p57W4lF1khWBkN3j4aePd7xDDIGzf6PmaWNBNQVJRCFal3E1V7F4JHffyBgtw3JPcNyYeGIvzm70xH9FBJBOgE3BmLu_9YyfliuT6YppPGhAHvjxrlf8mi5GUur75eyNW5-CKAXsk1_wNiK6y0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1490681108</pqid></control><display><type>article</type><title>Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans</title><source>Wiley</source><creator>Marshall, Vanessa J. ; Ramchandani, Vijay A. ; Kalu, Nnenna ; Kwagyan, John ; Scott, Denise M. ; Ferguson, Clifford L. ; Taylor, Robert E.</creator><creatorcontrib>Marshall, Vanessa J. ; Ramchandani, Vijay A. ; Kalu, Nnenna ; Kwagyan, John ; Scott, Denise M. ; Ferguson, Clifford L. ; Taylor, Robert E.</creatorcontrib><description>Introduction
The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers.
Materials
The sample included eighty‐seven 21‐ to 35‐year‐old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates.
Results
Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p < 0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p < 0.001). These observations were mediated by drinks per drinking day, gender, and FHA.
Conclusions
ADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day.</description><identifier>ISSN: 0145-6008</identifier><identifier>EISSN: 1530-0277</identifier><identifier>DOI: 10.1111/acer.12212</identifier><identifier>PMID: 23915245</identifier><identifier>CODEN: ACRSDM</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; African Americans - genetics ; African Descent Population ; Alcohol Dehydrogenase - genetics ; Alcohol Dehydrogenase Polymorphisms ; Alcohol Drinking - genetics ; Alcohol Drinking - metabolism ; Alcohol Elimination Rate ; Alcoholism - diagnosis ; Alcoholism - genetics ; Alcoholism - metabolism ; Breath Alcohol Clamping ; Breath tests ; Breath Tests - methods ; Ethanol - administration & dosage ; Ethanol - metabolism ; Female ; Humans ; Infusions, Intravenous ; Male ; Polymorphism, Genetic - genetics ; Sib Pair Analysis ; Siblings ; Young Adult</subject><ispartof>Alcoholism, clinical and experimental research, 2014-01, Vol.38 (1), p.51-59</ispartof><rights>Copyright © 2013 by the Research Society on Alcoholism</rights><rights>Copyright © 2013 by the Research Society on Alcoholism.</rights><rights>2014 Research Society on Alcoholism</rights><rights>Copyright © 2013 by the Research Society on Alcoholism. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4862-d1950f9640306fba41395defae089b2d7deda02af14793e72697acd9d15fc0533</citedby><cites>FETCH-LOGICAL-c4862-d1950f9640306fba41395defae089b2d7deda02af14793e72697acd9d15fc0533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23915245$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marshall, Vanessa J.</creatorcontrib><creatorcontrib>Ramchandani, Vijay A.</creatorcontrib><creatorcontrib>Kalu, Nnenna</creatorcontrib><creatorcontrib>Kwagyan, John</creatorcontrib><creatorcontrib>Scott, Denise M.</creatorcontrib><creatorcontrib>Ferguson, Clifford L.</creatorcontrib><creatorcontrib>Taylor, Robert E.</creatorcontrib><title>Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans</title><title>Alcoholism, clinical and experimental research</title><addtitle>Alcohol Clin Exp Res</addtitle><description>Introduction
The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers.
Materials
The sample included eighty‐seven 21‐ to 35‐year‐old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates.
Results
Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p < 0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p < 0.001). These observations were mediated by drinks per drinking day, gender, and FHA.
Conclusions
ADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day.</description><subject>Adult</subject><subject>African Americans - genetics</subject><subject>African Descent Population</subject><subject>Alcohol Dehydrogenase - genetics</subject><subject>Alcohol Dehydrogenase Polymorphisms</subject><subject>Alcohol Drinking - genetics</subject><subject>Alcohol Drinking - metabolism</subject><subject>Alcohol Elimination Rate</subject><subject>Alcoholism - diagnosis</subject><subject>Alcoholism - genetics</subject><subject>Alcoholism - metabolism</subject><subject>Breath Alcohol Clamping</subject><subject>Breath tests</subject><subject>Breath Tests - methods</subject><subject>Ethanol - administration & dosage</subject><subject>Ethanol - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Male</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Sib Pair Analysis</subject><subject>Siblings</subject><subject>Young Adult</subject><issn>0145-6008</issn><issn>1530-0277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNp9kV9v0zAUxS0EYmXwwgdAkXhDyri2888vSF0pY6gCVIH2aLnJ9eLhxMVOtvXb4y5rBS_45Vq-v3N8pEPIawpnNJ73qkZ_Rhmj7AmZ0ZxDCqwsn5IZ0CxPC4DqhLwI4QYAsqoonpMTxgXNWZbPyLC8VXZUg3F94nQytJhc9tqO2Ne4f5jb2rXOJh-x3TXeXWOvAibfnd11zm9bE7qQROkBW1rTmX6yW6sBQ2LiUntTqzg7fLiEl-SZVjbgq8d5Sn5-Wv5YfE5X3y4uF_NVWsecLG2oyEGLIgMOhd6ojHKRN6gVQiU2rCkbbBQwpWlWCo4lK0Sp6kY0NNc15Jyfkg-T73bcdNjU2A9eWbn1plN-J50y8t9Nb1p57W4lF1khWBkN3j4aePd7xDDIGzf6PmaWNBNQVJRCFal3E1V7F4JHffyBgtw3JPcNyYeGIvzm70xH9FBJBOgE3BmLu_9YyfliuT6YppPGhAHvjxrlf8mi5GUur75eyNW5-CKAXsk1_wNiK6y0</recordid><startdate>201401</startdate><enddate>201401</enddate><creator>Marshall, Vanessa J.</creator><creator>Ramchandani, Vijay A.</creator><creator>Kalu, Nnenna</creator><creator>Kwagyan, John</creator><creator>Scott, Denise M.</creator><creator>Ferguson, Clifford L.</creator><creator>Taylor, Robert E.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7TK</scope><scope>K7.</scope><scope>K9.</scope><scope>5PM</scope></search><sort><creationdate>201401</creationdate><title>Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans</title><author>Marshall, Vanessa J. ; Ramchandani, Vijay A. ; Kalu, Nnenna ; Kwagyan, John ; Scott, Denise M. ; Ferguson, Clifford L. ; Taylor, Robert E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4862-d1950f9640306fba41395defae089b2d7deda02af14793e72697acd9d15fc0533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>African Americans - genetics</topic><topic>African Descent Population</topic><topic>Alcohol Dehydrogenase - genetics</topic><topic>Alcohol Dehydrogenase Polymorphisms</topic><topic>Alcohol Drinking - genetics</topic><topic>Alcohol Drinking - metabolism</topic><topic>Alcohol Elimination Rate</topic><topic>Alcoholism - diagnosis</topic><topic>Alcoholism - genetics</topic><topic>Alcoholism - metabolism</topic><topic>Breath Alcohol Clamping</topic><topic>Breath tests</topic><topic>Breath Tests - methods</topic><topic>Ethanol - administration & dosage</topic><topic>Ethanol - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Male</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Sib Pair Analysis</topic><topic>Siblings</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marshall, Vanessa J.</creatorcontrib><creatorcontrib>Ramchandani, Vijay A.</creatorcontrib><creatorcontrib>Kalu, Nnenna</creatorcontrib><creatorcontrib>Kwagyan, John</creatorcontrib><creatorcontrib>Scott, Denise M.</creatorcontrib><creatorcontrib>Ferguson, Clifford L.</creatorcontrib><creatorcontrib>Taylor, Robert E.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alcoholism, clinical and experimental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marshall, Vanessa J.</au><au>Ramchandani, Vijay A.</au><au>Kalu, Nnenna</au><au>Kwagyan, John</au><au>Scott, Denise M.</au><au>Ferguson, Clifford L.</au><au>Taylor, Robert E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans</atitle><jtitle>Alcoholism, clinical and experimental research</jtitle><addtitle>Alcohol Clin Exp Res</addtitle><date>2014-01</date><risdate>2014</risdate><volume>38</volume><issue>1</issue><spage>51</spage><epage>59</epage><pages>51-59</pages><issn>0145-6008</issn><eissn>1530-0277</eissn><coden>ACRSDM</coden><abstract>Introduction
The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers.
Materials
The sample included eighty‐seven 21‐ to 35‐year‐old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates.
Results
Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p < 0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p < 0.001). These observations were mediated by drinks per drinking day, gender, and FHA.
Conclusions
ADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23915245</pmid><doi>10.1111/acer.12212</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult African Americans - genetics African Descent Population Alcohol Dehydrogenase - genetics Alcohol Dehydrogenase Polymorphisms Alcohol Drinking - genetics Alcohol Drinking - metabolism Alcohol Elimination Rate Alcoholism - diagnosis Alcoholism - genetics Alcoholism - metabolism Breath Alcohol Clamping Breath tests Breath Tests - methods Ethanol - administration & dosage Ethanol - metabolism Female Humans Infusions, Intravenous Male Polymorphism, Genetic - genetics Sib Pair Analysis Siblings Young Adult |
| title | Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans |
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