Smoking, cardiovascular risk factors and LRP2 gene variation: Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis
•Smoking after onset of PPMS is associated with increased disability.•Smoking after onset of PPMS is associated with cognitive impairment.•Smoking after PPMS onset is associated with lower myelin content in lesions.•Framingham risk score may be associated with atrophy of cortex.•The risk variant of...
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| Veröffentlicht in: | Multiple sclerosis and related disorders 2021-11, Vol.56, p.103296-103296, Article 103296 |
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| creator | Chow, Helene Højsgaard Talbot, Jacob Marstrand, Lisbet Lundell, Henrik Roman Siebner, Hartwig Bach Søndergaard, Helle Sellebjerg, Finn |
| description | •Smoking after onset of PPMS is associated with increased disability.•Smoking after onset of PPMS is associated with cognitive impairment.•Smoking after PPMS onset is associated with lower myelin content in lesions.•Framingham risk score may be associated with atrophy of cortex.•The risk variant of the LRP2 gene is associated with CI.
Smoking, cardiovascular risk factors, and genetic factors can have adverse effects in MS.
To determine if smoking after disease onset, cardiovascular risk factors, and genetic variants influence primary progressive MS (PPMS).
In this cross-sectional study, smoking habits, Framingham Risk Score (FRS), genetic variants, including the low-density lipoprotein receptor-related protein 2 (LRP2) SNP rs12988804 and MRI were collected in 60 PPMS trial participants. Disability and cognition were assessed with the Age-Related Multiple Sclerosis Severity (ARMSS) score, the Progressive-Onset MS Multiple Sclerosis Severity Score, and the Brief International Cognitive Assessment for MS.
Smoking after PPMS onset was significantly associated with higher ARMSS (95% CI 0.8–2.4, p = 0.00016) statistically significant after Bonferroni correction. Lower magnetization transfer ratio in lesions was also significantly associated with smoking after onset of PPMS after correction (95% CI -0.9–-4.4, p = 0.0035). Pack-years in people who smoked after onset was likewise significantly associated with higher ARMSS score (b = 0.06 95% CI 0.02–0.09, p = 0.0021) as well as lower Symbol Digit Modalities Test scores (b = -0.40; 95% CI -0.66–-0.13, p = 0.0037), both statistically significant after Bonferroni correction. The LRP2 risk allele was associated with decreased performance on the California Verbal Learning Test 2 after correction (CC vs. CT+TT 95% CI -14.2–-3.4, p = 0.0018).
If validated, these findings suggest that intervention regarding smoking may be beneficial in PPMS. If confirmed, assessment of the LRP2 gene variant may aid in the understanding of underlying pathological mechanisms in PPMS. |
| doi_str_mv | 10.1016/j.msard.2021.103296 |
| format | Article |
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Smoking, cardiovascular risk factors, and genetic factors can have adverse effects in MS.
To determine if smoking after disease onset, cardiovascular risk factors, and genetic variants influence primary progressive MS (PPMS).
In this cross-sectional study, smoking habits, Framingham Risk Score (FRS), genetic variants, including the low-density lipoprotein receptor-related protein 2 (LRP2) SNP rs12988804 and MRI were collected in 60 PPMS trial participants. Disability and cognition were assessed with the Age-Related Multiple Sclerosis Severity (ARMSS) score, the Progressive-Onset MS Multiple Sclerosis Severity Score, and the Brief International Cognitive Assessment for MS.
Smoking after PPMS onset was significantly associated with higher ARMSS (95% CI 0.8–2.4, p = 0.00016) statistically significant after Bonferroni correction. Lower magnetization transfer ratio in lesions was also significantly associated with smoking after onset of PPMS after correction (95% CI -0.9–-4.4, p = 0.0035). Pack-years in people who smoked after onset was likewise significantly associated with higher ARMSS score (b = 0.06 95% CI 0.02–0.09, p = 0.0021) as well as lower Symbol Digit Modalities Test scores (b = -0.40; 95% CI -0.66–-0.13, p = 0.0037), both statistically significant after Bonferroni correction. The LRP2 risk allele was associated with decreased performance on the California Verbal Learning Test 2 after correction (CC vs. CT+TT 95% CI -14.2–-3.4, p = 0.0018).
If validated, these findings suggest that intervention regarding smoking may be beneficial in PPMS. If confirmed, assessment of the LRP2 gene variant may aid in the understanding of underlying pathological mechanisms in PPMS.</description><identifier>ISSN: 2211-0348</identifier><identifier>EISSN: 2211-0356</identifier><identifier>DOI: 10.1016/j.msard.2021.103296</identifier><identifier>PMID: 34678704</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Age-related multiple sclerosis severity score ; Brain - diagnostic imaging ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - genetics ; Cognition ; Cross-Sectional Studies ; Framingham risk score ; Heart Disease Risk Factors ; Humans ; Low Density Lipoprotein Receptor-Related Protein-2 ; Multiple Sclerosis - epidemiology ; Multiple Sclerosis - genetics ; Multiple Sclerosis, Chronic Progressive ; Primary progressive multiple sclerosis ; Risk Factors ; Severity of Illness Index ; Smoking ; Smoking - genetics</subject><ispartof>Multiple sclerosis and related disorders, 2021-11, Vol.56, p.103296-103296, Article 103296</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-cf990844904218754ed69ca9a475b7c4259800a250e75891a45d8ad0b14f55773</citedby><cites>FETCH-LOGICAL-c359t-cf990844904218754ed69ca9a475b7c4259800a250e75891a45d8ad0b14f55773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34678704$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chow, Helene Højsgaard</creatorcontrib><creatorcontrib>Talbot, Jacob</creatorcontrib><creatorcontrib>Marstrand, Lisbet</creatorcontrib><creatorcontrib>Lundell, Henrik</creatorcontrib><creatorcontrib>Roman Siebner, Hartwig</creatorcontrib><creatorcontrib>Bach Søndergaard, Helle</creatorcontrib><creatorcontrib>Sellebjerg, Finn</creatorcontrib><title>Smoking, cardiovascular risk factors and LRP2 gene variation: Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis</title><title>Multiple sclerosis and related disorders</title><addtitle>Mult Scler Relat Disord</addtitle><description>•Smoking after onset of PPMS is associated with increased disability.•Smoking after onset of PPMS is associated with cognitive impairment.•Smoking after PPMS onset is associated with lower myelin content in lesions.•Framingham risk score may be associated with atrophy of cortex.•The risk variant of the LRP2 gene is associated with CI.
Smoking, cardiovascular risk factors, and genetic factors can have adverse effects in MS.
To determine if smoking after disease onset, cardiovascular risk factors, and genetic variants influence primary progressive MS (PPMS).
In this cross-sectional study, smoking habits, Framingham Risk Score (FRS), genetic variants, including the low-density lipoprotein receptor-related protein 2 (LRP2) SNP rs12988804 and MRI were collected in 60 PPMS trial participants. Disability and cognition were assessed with the Age-Related Multiple Sclerosis Severity (ARMSS) score, the Progressive-Onset MS Multiple Sclerosis Severity Score, and the Brief International Cognitive Assessment for MS.
Smoking after PPMS onset was significantly associated with higher ARMSS (95% CI 0.8–2.4, p = 0.00016) statistically significant after Bonferroni correction. Lower magnetization transfer ratio in lesions was also significantly associated with smoking after onset of PPMS after correction (95% CI -0.9–-4.4, p = 0.0035). Pack-years in people who smoked after onset was likewise significantly associated with higher ARMSS score (b = 0.06 95% CI 0.02–0.09, p = 0.0021) as well as lower Symbol Digit Modalities Test scores (b = -0.40; 95% CI -0.66–-0.13, p = 0.0037), both statistically significant after Bonferroni correction. The LRP2 risk allele was associated with decreased performance on the California Verbal Learning Test 2 after correction (CC vs. CT+TT 95% CI -14.2–-3.4, p = 0.0018).
If validated, these findings suggest that intervention regarding smoking may be beneficial in PPMS. If confirmed, assessment of the LRP2 gene variant may aid in the understanding of underlying pathological mechanisms in PPMS.</description><subject>Age-related multiple sclerosis severity score</subject><subject>Brain - diagnostic imaging</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Cognition</subject><subject>Cross-Sectional Studies</subject><subject>Framingham risk score</subject><subject>Heart Disease Risk Factors</subject><subject>Humans</subject><subject>Low Density Lipoprotein Receptor-Related Protein-2</subject><subject>Multiple Sclerosis - epidemiology</subject><subject>Multiple Sclerosis - genetics</subject><subject>Multiple Sclerosis, Chronic Progressive</subject><subject>Primary progressive multiple sclerosis</subject><subject>Risk Factors</subject><subject>Severity of Illness Index</subject><subject>Smoking</subject><subject>Smoking - genetics</subject><issn>2211-0348</issn><issn>2211-0356</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Udtu1DAQjRCIVqVfgIT8yAO72I4dx0g8VBU3aSUQl2fL60yW2SZx8ThB_S2-EG936SPzMhedc2ZGp6qeC74WXDSv9-uRfOrWkktRJrW0zaPqXEohVrzWzeOHWrVn1SXRnpdotFCNeFqd1aoxreHqvPrzbYw3OO1esVDkMC6ewjz4xBLSDet9yDER81PHNl-_SLaDCdjiE_qMcXrDrohiODbEfmP-yTok8ASMYIGE-a4Ix92EGRdg_TyFA_Reb5s8ToxymkOeE7DS3CYcfborOe4SEB044zxkvB2KYBggRUJ6Vj3p_UBwecoX1Y_3775ff1xtPn_4dH21WYVa27wKvbW8VcpyJUVrtIKuscFbr4zemqCkti3nXmoORrdWeKW71nd8K1SvtTH1RfXyqFvO-TUDZTciBRgGP0GcyUndKmNsq22B1kdoKBdSgt6dXnGCu4Nfbu_u_XIHv9zRr8J6cVowb0foHjj_3CmAt0cAlDcXhOQoIEwBOkwQsusi_nfBXzW2qwU</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Chow, Helene Højsgaard</creator><creator>Talbot, Jacob</creator><creator>Marstrand, Lisbet</creator><creator>Lundell, Henrik</creator><creator>Roman Siebner, Hartwig</creator><creator>Bach Søndergaard, Helle</creator><creator>Sellebjerg, Finn</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>202111</creationdate><title>Smoking, cardiovascular risk factors and LRP2 gene variation: Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis</title><author>Chow, Helene Højsgaard ; Talbot, Jacob ; Marstrand, Lisbet ; Lundell, Henrik ; Roman Siebner, Hartwig ; Bach Søndergaard, Helle ; Sellebjerg, Finn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-cf990844904218754ed69ca9a475b7c4259800a250e75891a45d8ad0b14f55773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Age-related multiple sclerosis severity score</topic><topic>Brain - diagnostic imaging</topic><topic>Cardiovascular Diseases - epidemiology</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Cognition</topic><topic>Cross-Sectional Studies</topic><topic>Framingham risk score</topic><topic>Heart Disease Risk Factors</topic><topic>Humans</topic><topic>Low Density Lipoprotein Receptor-Related Protein-2</topic><topic>Multiple Sclerosis - epidemiology</topic><topic>Multiple Sclerosis - genetics</topic><topic>Multiple Sclerosis, Chronic Progressive</topic><topic>Primary progressive multiple sclerosis</topic><topic>Risk Factors</topic><topic>Severity of Illness Index</topic><topic>Smoking</topic><topic>Smoking - genetics</topic><toplevel>online_resources</toplevel><creatorcontrib>Chow, Helene Højsgaard</creatorcontrib><creatorcontrib>Talbot, Jacob</creatorcontrib><creatorcontrib>Marstrand, Lisbet</creatorcontrib><creatorcontrib>Lundell, Henrik</creatorcontrib><creatorcontrib>Roman Siebner, Hartwig</creatorcontrib><creatorcontrib>Bach Søndergaard, Helle</creatorcontrib><creatorcontrib>Sellebjerg, Finn</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Multiple sclerosis and related disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chow, Helene Højsgaard</au><au>Talbot, Jacob</au><au>Marstrand, Lisbet</au><au>Lundell, Henrik</au><au>Roman Siebner, Hartwig</au><au>Bach Søndergaard, Helle</au><au>Sellebjerg, Finn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Smoking, cardiovascular risk factors and LRP2 gene variation: Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis</atitle><jtitle>Multiple sclerosis and related disorders</jtitle><addtitle>Mult Scler Relat Disord</addtitle><date>2021-11</date><risdate>2021</risdate><volume>56</volume><spage>103296</spage><epage>103296</epage><pages>103296-103296</pages><artnum>103296</artnum><issn>2211-0348</issn><eissn>2211-0356</eissn><abstract>•Smoking after onset of PPMS is associated with increased disability.•Smoking after onset of PPMS is associated with cognitive impairment.•Smoking after PPMS onset is associated with lower myelin content in lesions.•Framingham risk score may be associated with atrophy of cortex.•The risk variant of the LRP2 gene is associated with CI.
Smoking, cardiovascular risk factors, and genetic factors can have adverse effects in MS.
To determine if smoking after disease onset, cardiovascular risk factors, and genetic variants influence primary progressive MS (PPMS).
In this cross-sectional study, smoking habits, Framingham Risk Score (FRS), genetic variants, including the low-density lipoprotein receptor-related protein 2 (LRP2) SNP rs12988804 and MRI were collected in 60 PPMS trial participants. Disability and cognition were assessed with the Age-Related Multiple Sclerosis Severity (ARMSS) score, the Progressive-Onset MS Multiple Sclerosis Severity Score, and the Brief International Cognitive Assessment for MS.
Smoking after PPMS onset was significantly associated with higher ARMSS (95% CI 0.8–2.4, p = 0.00016) statistically significant after Bonferroni correction. Lower magnetization transfer ratio in lesions was also significantly associated with smoking after onset of PPMS after correction (95% CI -0.9–-4.4, p = 0.0035). Pack-years in people who smoked after onset was likewise significantly associated with higher ARMSS score (b = 0.06 95% CI 0.02–0.09, p = 0.0021) as well as lower Symbol Digit Modalities Test scores (b = -0.40; 95% CI -0.66–-0.13, p = 0.0037), both statistically significant after Bonferroni correction. The LRP2 risk allele was associated with decreased performance on the California Verbal Learning Test 2 after correction (CC vs. CT+TT 95% CI -14.2–-3.4, p = 0.0018).
If validated, these findings suggest that intervention regarding smoking may be beneficial in PPMS. If confirmed, assessment of the LRP2 gene variant may aid in the understanding of underlying pathological mechanisms in PPMS.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34678704</pmid><doi>10.1016/j.msard.2021.103296</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Age-related multiple sclerosis severity score Brain - diagnostic imaging Cardiovascular Diseases - epidemiology Cardiovascular Diseases - genetics Cognition Cross-Sectional Studies Framingham risk score Heart Disease Risk Factors Humans Low Density Lipoprotein Receptor-Related Protein-2 Multiple Sclerosis - epidemiology Multiple Sclerosis - genetics Multiple Sclerosis, Chronic Progressive Primary progressive multiple sclerosis Risk Factors Severity of Illness Index Smoking Smoking - genetics |
| title | Smoking, cardiovascular risk factors and LRP2 gene variation: Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis |
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