Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene
Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R...
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| Veröffentlicht in: | The pharmacogenomics journal 2013-06, Vol.13 (3), p.272-279 |
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| creator | Chowdhury, N I Tiwari, A K Souza, R P Zai, C C Shaikh, S A Chen, S Liu, F Lieberman, J A Meltzer, H Y Malhotra, A K Kennedy, J L Müller, D J |
| description | Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (
r
2
⩽0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (
P
=0.027,
n
=69). These observations were marginal after correction for multiple testing. We performed
in vitro
electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings. |
| doi_str_mv | 10.1038/tpj.2011.66 |
| format | Article |
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r
2
⩽0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (
P
=0.027,
n
=69). These observations were marginal after correction for multiple testing. We performed
in vitro
electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.</description><identifier>ISSN: 1470-269X</identifier><identifier>EISSN: 1473-1150</identifier><identifier>DOI: 10.1038/tpj.2011.66</identifier><identifier>PMID: 22310352</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/699/2743/393 ; 692/699/476/1799 ; 692/700/565/1436/434 ; Adult ; Alleles ; Antipsychotic Agents - administration & dosage ; Antipsychotic Agents - adverse effects ; Antipsychotic drugs ; Antipsychotics ; Binding sites ; Biomedical and Life Sciences ; Biomedicine ; Clozapine ; Clozapine - administration & dosage ; Clozapine - adverse effects ; Electrophoretic mobility ; Electrophoretic Mobility Shift Assay ; Female ; Gene Expression ; Genetic aspects ; Genetic Association Studies ; Human Genetics ; Humans ; Male ; Melanocortin ; Melanocortin MC4 receptors ; Mental disorders ; Metabolic syndrome ; Middle Aged ; Oncology ; original-article ; Patients ; Pharmacotherapy ; Polymorphism, Single Nucleotide - genetics ; Psychopharmacology ; Psychotropic drugs ; Receptor, Melanocortin, Type 4 - genetics ; Schizophrenia ; Schizophrenia - complications ; Schizophrenia - drug therapy ; Schizophrenia - genetics ; Single-nucleotide polymorphism ; Weight gain ; Weight Gain - drug effects ; Weight Gain - genetics</subject><ispartof>The pharmacogenomics journal, 2013-06, Vol.13 (3), p.272-279</ispartof><rights>Macmillan Publishers Limited 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2013</rights><rights>Macmillan Publishers Limited 2013.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-574e8d1b9f4f144aaf35efb55b36eb0b828123d575db99d5be7c74580ab6e3503</citedby><cites>FETCH-LOGICAL-c519t-574e8d1b9f4f144aaf35efb55b36eb0b828123d575db99d5be7c74580ab6e3503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22310352$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chowdhury, N I</creatorcontrib><creatorcontrib>Tiwari, A K</creatorcontrib><creatorcontrib>Souza, R P</creatorcontrib><creatorcontrib>Zai, C C</creatorcontrib><creatorcontrib>Shaikh, S A</creatorcontrib><creatorcontrib>Chen, S</creatorcontrib><creatorcontrib>Liu, F</creatorcontrib><creatorcontrib>Lieberman, J A</creatorcontrib><creatorcontrib>Meltzer, H Y</creatorcontrib><creatorcontrib>Malhotra, A K</creatorcontrib><creatorcontrib>Kennedy, J L</creatorcontrib><creatorcontrib>Müller, D J</creatorcontrib><title>Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene</title><title>The pharmacogenomics journal</title><addtitle>Pharmacogenomics J</addtitle><addtitle>Pharmacogenomics J</addtitle><description>Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (
r
2
⩽0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (
P
=0.027,
n
=69). These observations were marginal after correction for multiple testing. We performed
in vitro
electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.</description><subject>692/699/2743/393</subject><subject>692/699/476/1799</subject><subject>692/700/565/1436/434</subject><subject>Adult</subject><subject>Alleles</subject><subject>Antipsychotic Agents - administration & dosage</subject><subject>Antipsychotic Agents - adverse effects</subject><subject>Antipsychotic drugs</subject><subject>Antipsychotics</subject><subject>Binding sites</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Clozapine</subject><subject>Clozapine - administration & dosage</subject><subject>Clozapine - adverse effects</subject><subject>Electrophoretic mobility</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Melanocortin</subject><subject>Melanocortin MC4 receptors</subject><subject>Mental disorders</subject><subject>Metabolic syndrome</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patients</subject><subject>Pharmacotherapy</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Psychopharmacology</subject><subject>Psychotropic drugs</subject><subject>Receptor, Melanocortin, Type 4 - genetics</subject><subject>Schizophrenia</subject><subject>Schizophrenia - complications</subject><subject>Schizophrenia - drug therapy</subject><subject>Schizophrenia - genetics</subject><subject>Single-nucleotide polymorphism</subject><subject>Weight gain</subject><subject>Weight Gain - drug effects</subject><subject>Weight Gain - genetics</subject><issn>1470-269X</issn><issn>1473-1150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqN0kmLFDEUAOBCFGfRk3cp8CJotdlTdRwGHYUBLwreQpZX1Wm6kjZJMfS_n7Q948YgkkNC8r0l8JrmBUYrjGj_ruw2K4IwXgnxqDnFTNIOY44e_zijjojh20lzlvMGISyw7J82J4TQGsrJabO-ggDF21bnHK3XxcfQ5rK4fWug3ACEVofid3lv17G6zge3WHDtDfhpXdpJ-4NwbVlDO8NWh2hjKj50rE1gYVdiaqda41nzZNTbDM_v9vPm64f3Xy4_dtefrz5dXlx3luOhdFwy6B02w8hGzJjWI-UwGs4NFWCQ6UmPCXVccmeGwXED0krGe6SNAMoRPW9eH_PuUvy-QC5q9tnCtnYGcckKU0kQ54z1_0Grk5LSodJXf9FNXFKoH1FEMCyxFIP8l6q5GBJSSv5LTXoLyocxlqTtobS6oJQILgUjVa0eUHU5mL2NAUZf7_8IeHMMsCnmnGBUu-RnnfYKI3UYFFUHRR0GRQlR9cu7Vhczg_tp7yejgrdHkOtTmCD99pcH8t0Cwu_FcQ</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>Chowdhury, N I</creator><creator>Tiwari, A K</creator><creator>Souza, R P</creator><creator>Zai, C C</creator><creator>Shaikh, S A</creator><creator>Chen, S</creator><creator>Liu, F</creator><creator>Lieberman, J A</creator><creator>Meltzer, H Y</creator><creator>Malhotra, A K</creator><creator>Kennedy, J L</creator><creator>Müller, D J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20130601</creationdate><title>Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene</title><author>Chowdhury, N I ; Tiwari, A K ; Souza, R P ; Zai, C C ; Shaikh, S A ; Chen, S ; Liu, F ; Lieberman, J A ; Meltzer, H Y ; Malhotra, A K ; Kennedy, J L ; Müller, D J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-574e8d1b9f4f144aaf35efb55b36eb0b828123d575db99d5be7c74580ab6e3503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>692/699/2743/393</topic><topic>692/699/476/1799</topic><topic>692/700/565/1436/434</topic><topic>Adult</topic><topic>Alleles</topic><topic>Antipsychotic Agents - administration & dosage</topic><topic>Antipsychotic Agents - adverse effects</topic><topic>Antipsychotic drugs</topic><topic>Antipsychotics</topic><topic>Binding sites</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Clozapine</topic><topic>Clozapine - administration & dosage</topic><topic>Clozapine - adverse effects</topic><topic>Electrophoretic mobility</topic><topic>Electrophoretic Mobility Shift Assay</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Genetic aspects</topic><topic>Genetic Association Studies</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Melanocortin</topic><topic>Melanocortin MC4 receptors</topic><topic>Mental disorders</topic><topic>Metabolic syndrome</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>original-article</topic><topic>Patients</topic><topic>Pharmacotherapy</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Psychopharmacology</topic><topic>Psychotropic drugs</topic><topic>Receptor, Melanocortin, Type 4 - genetics</topic><topic>Schizophrenia</topic><topic>Schizophrenia - complications</topic><topic>Schizophrenia - drug therapy</topic><topic>Schizophrenia - genetics</topic><topic>Single-nucleotide polymorphism</topic><topic>Weight gain</topic><topic>Weight Gain - drug effects</topic><topic>Weight Gain - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chowdhury, N I</creatorcontrib><creatorcontrib>Tiwari, A K</creatorcontrib><creatorcontrib>Souza, R P</creatorcontrib><creatorcontrib>Zai, C C</creatorcontrib><creatorcontrib>Shaikh, S A</creatorcontrib><creatorcontrib>Chen, S</creatorcontrib><creatorcontrib>Liu, F</creatorcontrib><creatorcontrib>Lieberman, J A</creatorcontrib><creatorcontrib>Meltzer, H Y</creatorcontrib><creatorcontrib>Malhotra, A K</creatorcontrib><creatorcontrib>Kennedy, J L</creatorcontrib><creatorcontrib>Müller, D J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The pharmacogenomics journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chowdhury, N I</au><au>Tiwari, A K</au><au>Souza, R P</au><au>Zai, C C</au><au>Shaikh, S A</au><au>Chen, S</au><au>Liu, F</au><au>Lieberman, J A</au><au>Meltzer, H Y</au><au>Malhotra, A K</au><au>Kennedy, J L</au><au>Müller, D J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene</atitle><jtitle>The pharmacogenomics journal</jtitle><stitle>Pharmacogenomics J</stitle><addtitle>Pharmacogenomics J</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>13</volume><issue>3</issue><spage>272</spage><epage>279</epage><pages>272-279</pages><issn>1470-269X</issn><eissn>1473-1150</eissn><abstract>Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (
r
2
⩽0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (
P
=0.027,
n
=69). These observations were marginal after correction for multiple testing. We performed
in vitro
electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22310352</pmid><doi>10.1038/tpj.2011.66</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The pharmacogenomics journal, 2013-06, Vol.13 (3), p.272-279 |
| issn | 1470-269X 1473-1150 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 692/699/2743/393 692/699/476/1799 692/700/565/1436/434 Adult Alleles Antipsychotic Agents - administration & dosage Antipsychotic Agents - adverse effects Antipsychotic drugs Antipsychotics Binding sites Biomedical and Life Sciences Biomedicine Clozapine Clozapine - administration & dosage Clozapine - adverse effects Electrophoretic mobility Electrophoretic Mobility Shift Assay Female Gene Expression Genetic aspects Genetic Association Studies Human Genetics Humans Male Melanocortin Melanocortin MC4 receptors Mental disorders Metabolic syndrome Middle Aged Oncology original-article Patients Pharmacotherapy Polymorphism, Single Nucleotide - genetics Psychopharmacology Psychotropic drugs Receptor, Melanocortin, Type 4 - genetics Schizophrenia Schizophrenia - complications Schizophrenia - drug therapy Schizophrenia - genetics Single-nucleotide polymorphism Weight gain Weight Gain - drug effects Weight Gain - genetics |
| title | Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene |
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