Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis
OBJECTIVE:We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS). METHODS:We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with p...
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| Veröffentlicht in: | Neurology 2014-03, Vol.82 (10), p.865-872 |
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| creator | Hedström, Anna Karin Lima Bomfim, Izaura Barcellos, Lisa Gianfrancesco, Milena Schaefer, Catherine Kockum, Ingrid Olsson, Tomas Alfredsson, Lars |
| description | OBJECTIVE:We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS).
METHODS:We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction.
RESULTS:In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5–35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1–46.8).
CONCLUSIONS:We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule–restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease. |
| doi_str_mv | 10.1212/WNL.0000000000000203 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_523800</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1635038235</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5583-d3e03b877d0e8440833f87ecd1f9cc83e964040e2114103f48833a820c55de763</originalsourceid><addsrcrecordid>eNp9kk1vEzEQhi0EoiHwDxDyBYnLFn_uei9IVQVtpQguILhZjnc2MXHsYHuJ8u_rKqG0HPDF1szzjsfzGqHXlJxTRtn7758X5-ThYoQ_QTMqWdu0nP14imY1phquOnWGXuT8k5Ca7Prn6IwJSUgruhnSN6FAMra4GPASyh4gYDNED9lCKDguIbtywCYM-HpxgZPLG7yCABm7gMsaMFSpj6sDjiPeTr64nQecrYcUs8sv0bPR-AyvTvscffv08evldbP4cnVzebForJSKNwMHwpeq6wYCSgiiOB9VB3agY2-t4tC3gggCjFJBCR-FqoRRjFT5AF3L56g51s172E1LvUtua9JBR-P0KbSpJ9CScUVI5T8c-ZrZwnD31mT8I9njTHBrvYq_Ne9l39Uic_TuVCDFXxPkoreujsx7EyBOWdOWS8IV47Ki4ojaOpKcYLy_hhJ956WuXup_vayyNw9bvBf9Ma8Cb0-Aydb4MZlgXf7LKS7rZ1CVU0duH301O2_8tIek12B8Wf-_h1vzIrlM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1635038235</pqid></control><display><type>article</type><title>Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>SWEPUB Freely available online</source><source>Journals@Ovid Complete</source><creator>Hedström, Anna Karin ; Lima Bomfim, Izaura ; Barcellos, Lisa ; Gianfrancesco, Milena ; Schaefer, Catherine ; Kockum, Ingrid ; Olsson, Tomas ; Alfredsson, Lars</creator><creatorcontrib>Hedström, Anna Karin ; Lima Bomfim, Izaura ; Barcellos, Lisa ; Gianfrancesco, Milena ; Schaefer, Catherine ; Kockum, Ingrid ; Olsson, Tomas ; Alfredsson, Lars</creatorcontrib><description>OBJECTIVE:We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS).
METHODS:We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction.
RESULTS:In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5–35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1–46.8).
CONCLUSIONS:We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule–restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease.</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/WNL.0000000000000203</identifier><identifier>PMID: 24500647</identifier><identifier>CODEN: NEURAI</identifier><language>eng</language><publisher>Hagerstown, MD: American Academy of Neurology</publisher><subject>Adolescent ; Adult ; Aged ; Biological and medical sciences ; Body Mass Index ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; HLA-A2 Antigen - genetics ; HLA-DRB1 Chains - genetics ; Humans ; Immunomodulators ; Male ; Medical sciences ; Metabolic diseases ; Middle Aged ; Multiple Sclerosis - epidemiology ; Multiple Sclerosis - etiology ; Multiple Sclerosis - genetics ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Neurology ; Obesity ; Pediatric Obesity - epidemiology ; Pediatric Obesity - genetics ; Pharmacology. Drug treatments ; Risk Factors ; Young Adult</subject><ispartof>Neurology, 2014-03, Vol.82 (10), p.865-872</ispartof><rights>2014 American Academy of Neurology</rights><rights>2015 INIST-CNRS</rights><rights>2014 American Academy of Neurology 2014 American Academy of Neurology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5583-d3e03b877d0e8440833f87ecd1f9cc83e964040e2114103f48833a820c55de763</citedby><cites>FETCH-LOGICAL-c5583-d3e03b877d0e8440833f87ecd1f9cc83e964040e2114103f48833a820c55de763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28355268$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24500647$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:129110717$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Hedström, Anna Karin</creatorcontrib><creatorcontrib>Lima Bomfim, Izaura</creatorcontrib><creatorcontrib>Barcellos, Lisa</creatorcontrib><creatorcontrib>Gianfrancesco, Milena</creatorcontrib><creatorcontrib>Schaefer, Catherine</creatorcontrib><creatorcontrib>Kockum, Ingrid</creatorcontrib><creatorcontrib>Olsson, Tomas</creatorcontrib><creatorcontrib>Alfredsson, Lars</creatorcontrib><title>Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis</title><title>Neurology</title><addtitle>Neurology</addtitle><description>OBJECTIVE:We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS).
METHODS:We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction.
RESULTS:In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5–35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1–46.8).
CONCLUSIONS:We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule–restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Body Mass Index</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>HLA-A2 Antigen - genetics</subject><subject>HLA-DRB1 Chains - genetics</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - epidemiology</subject><subject>Multiple Sclerosis - etiology</subject><subject>Multiple Sclerosis - genetics</subject><subject>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</subject><subject>Neurology</subject><subject>Obesity</subject><subject>Pediatric Obesity - epidemiology</subject><subject>Pediatric Obesity - genetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Risk Factors</subject><subject>Young Adult</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9kk1vEzEQhi0EoiHwDxDyBYnLFn_uei9IVQVtpQguILhZjnc2MXHsYHuJ8u_rKqG0HPDF1szzjsfzGqHXlJxTRtn7758X5-ThYoQ_QTMqWdu0nP14imY1phquOnWGXuT8k5Ca7Prn6IwJSUgruhnSN6FAMra4GPASyh4gYDNED9lCKDguIbtywCYM-HpxgZPLG7yCABm7gMsaMFSpj6sDjiPeTr64nQecrYcUs8sv0bPR-AyvTvscffv08evldbP4cnVzebForJSKNwMHwpeq6wYCSgiiOB9VB3agY2-t4tC3gggCjFJBCR-FqoRRjFT5AF3L56g51s172E1LvUtua9JBR-P0KbSpJ9CScUVI5T8c-ZrZwnD31mT8I9njTHBrvYq_Ne9l39Uic_TuVCDFXxPkoreujsx7EyBOWdOWS8IV47Ki4ojaOpKcYLy_hhJ956WuXup_vayyNw9bvBf9Ma8Cb0-Aydb4MZlgXf7LKS7rZ1CVU0duH301O2_8tIek12B8Wf-_h1vzIrlM</recordid><startdate>20140311</startdate><enddate>20140311</enddate><creator>Hedström, Anna Karin</creator><creator>Lima Bomfim, Izaura</creator><creator>Barcellos, Lisa</creator><creator>Gianfrancesco, Milena</creator><creator>Schaefer, Catherine</creator><creator>Kockum, Ingrid</creator><creator>Olsson, Tomas</creator><creator>Alfredsson, Lars</creator><general>American Academy of Neurology</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20140311</creationdate><title>Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis</title><author>Hedström, Anna Karin ; Lima Bomfim, Izaura ; Barcellos, Lisa ; Gianfrancesco, Milena ; Schaefer, Catherine ; Kockum, Ingrid ; Olsson, Tomas ; Alfredsson, Lars</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5583-d3e03b877d0e8440833f87ecd1f9cc83e964040e2114103f48833a820c55de763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Body Mass Index</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>HLA-A2 Antigen - genetics</topic><topic>HLA-DRB1 Chains - genetics</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis - epidemiology</topic><topic>Multiple Sclerosis - etiology</topic><topic>Multiple Sclerosis - genetics</topic><topic>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</topic><topic>Neurology</topic><topic>Obesity</topic><topic>Pediatric Obesity - epidemiology</topic><topic>Pediatric Obesity - genetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Risk Factors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hedström, Anna Karin</creatorcontrib><creatorcontrib>Lima Bomfim, Izaura</creatorcontrib><creatorcontrib>Barcellos, Lisa</creatorcontrib><creatorcontrib>Gianfrancesco, Milena</creatorcontrib><creatorcontrib>Schaefer, Catherine</creatorcontrib><creatorcontrib>Kockum, Ingrid</creatorcontrib><creatorcontrib>Olsson, Tomas</creatorcontrib><creatorcontrib>Alfredsson, Lars</creatorcontrib><collection>Pascal-Francis</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hedström, Anna Karin</au><au>Lima Bomfim, Izaura</au><au>Barcellos, Lisa</au><au>Gianfrancesco, Milena</au><au>Schaefer, Catherine</au><au>Kockum, Ingrid</au><au>Olsson, Tomas</au><au>Alfredsson, Lars</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>2014-03-11</date><risdate>2014</risdate><volume>82</volume><issue>10</issue><spage>865</spage><epage>872</epage><pages>865-872</pages><issn>0028-3878</issn><eissn>1526-632X</eissn><coden>NEURAI</coden><abstract>OBJECTIVE:We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS).
METHODS:We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction.
RESULTS:In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5–35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1–46.8).
CONCLUSIONS:We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule–restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease.</abstract><cop>Hagerstown, MD</cop><pub>American Academy of Neurology</pub><pmid>24500647</pmid><doi>10.1212/WNL.0000000000000203</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Alma/SFX Local Collection; SWEPUB Freely available online; Journals@Ovid Complete |
| subjects | Adolescent Adult Aged Biological and medical sciences Body Mass Index Case-Control Studies Female Genetic Predisposition to Disease Genotype HLA-A2 Antigen - genetics HLA-DRB1 Chains - genetics Humans Immunomodulators Male Medical sciences Metabolic diseases Middle Aged Multiple Sclerosis - epidemiology Multiple Sclerosis - etiology Multiple Sclerosis - genetics Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Neurology Obesity Pediatric Obesity - epidemiology Pediatric Obesity - genetics Pharmacology. Drug treatments Risk Factors Young Adult |
| title | Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis |
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