{"paper_id":"3e8b8444-5da3-4355-b9ff-15bf52623708","body_text":"A Pilot Case-Control Study of Obesity as a State of Metaflammation: Association with Toll-Like Receptor 2 (Arg753Gln) Gene Polymorphism | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Pilot Case-Control Study of Obesity as a State of Metaflammation: Association with Toll-Like Receptor 2 (Arg753Gln) Gene Polymorphism Shaimaa H. Fouad, Mai Eldeeb, Shereen A. Baioumy, Sara I. Taha, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3310166/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jan, 2025 Read the published version in Scientific Reports → Version 2 posted You are reading this latest preprint version Show more versions Abstract Background: Obesity is a worldwide health issue linked to chronic metabolic low-grade inflammation (metaflammation) causing multiple obesity-related comorbid conditions. Several mediators were related to this metaflammatory process. Objectives: To assess the serum levels of leptin, wingless integration site family member 5A (Wnt5a), and tumor necrosis factor-alpha (TNF-α) as markers of obesity-associated metaflammation and investigate their association with toll-like receptors2 (TLR2) gene (Arg753Gln) single nucleotide polymorphism (SNP) among Egyptian females. Methods: This pilot case-control study included 60 females with obesity and 30 matched controls. Serum levels of leptin, Wnt5a, and TNF-α were assessed by ELISA, while TLR2 (Arg753Gln) genotyping was done by PCR-RFLP. The laboratory and anthropometric data of both groups were compared and correlated. Results: Serum leptin, Wnt5a, and TNF-α showed significantly higher levels in females with obesity and a significant increase with higher classes of obesity. They showed positive correlations with each other and with body weight, body mass index, fat mass index, erythrocyte sedimentation rate, and waist and hip circumferences. Only TNF-α and Wnt5a were associated with metabolic syndrome (MetS) among the obesity group, with Wnt5a being the only independent risk factor for MetS. According to TLR2 (Arg753Gln) SNP, the homozygous GG genotype was associated with elevated levels of TNF-α, leptin, and Wnt5a compared to the heterozygous GA genotype, and it was associated with MetS among the obesity group. The frequencies of the heterozygous GA genotype and the A allele were higher among the obesity group without MetS than those with MetS. Conclusion : Serum leptin, Wnt5a, and TNF-α are significantly higher in women with obesity and the A allele of TLR2 (Arg753Gln) SNP is considered protective against MetS among them. Inflammation Leptin Obesity Target therapy TLR2 TNF-α Wnt5a Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Jan, 2025 Read the published version in Scientific Reports → Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-3310166\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":230175395,\"identity\":\"ad15025a-cdb7-40d5-a2b1-e2df9c88f130\",\"order_by\":0,\"name\":\"Shaimaa H. Fouad\",\"email\":\"data:image/png;base64,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\",\"orcid\":\"\",\"institution\":\"Ain- Shams University\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shaimaa\",\"middleName\":\"H.\",\"lastName\":\"Fouad\",\"suffix\":\"\"},{\"id\":230175396,\"identity\":\"6e7005d7-84d9-4f3d-87e3-3bf1db68a156\",\"order_by\":1,\"name\":\"Mai Eldeeb\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Ain- Shams University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Mai\",\"middleName\":\"\",\"lastName\":\"Eldeeb\",\"suffix\":\"\"},{\"id\":230175397,\"identity\":\"d93f37c6-ad60-40ee-ba41-fab96982cb65\",\"order_by\":2,\"name\":\"Shereen A. 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Ibrahim\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Ain-Shams University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Rehab\",\"middleName\":\"A.\",\"lastName\":\"Ibrahim\",\"suffix\":\"\"},{\"id\":230175400,\"identity\":\"dd471b8a-eaae-4dcd-8839-a825235445c4\",\"order_by\":5,\"name\":\"Aya Elgendy\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Ain- Shams University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Aya\",\"middleName\":\"\",\"lastName\":\"Elgendy\",\"suffix\":\"\"},{\"id\":230175401,\"identity\":\"06b803f1-e67d-4b2d-8c1d-9c2f6357edec\",\"order_by\":6,\"name\":\"Marwa H.M. 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Roman\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Ain- Shams University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sylvia\",\"middleName\":\"W.\",\"lastName\":\"Roman\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2023-08-30 12:29:16\",\"currentVersionCode\":2,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-3310166/v2\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-3310166/v2\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1038/s41598-025-85470-9\",\"type\":\"published\",\"date\":\"2025-01-21T00:00:00+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":74467157,\"identity\":\"fd8bb314-bf94-4483-84d3-9a1906ea8fac\",\"added_by\":\"auto\",\"created_at\":\"2025-01-22 14:28:18\",\"extension\":\"pdf\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":586728,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"ObesityMetaflammationTLR2.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3310166/v2_covered_d4626b54-1a44-433f-8ba2-2b043597cc66.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"\\u003cp\\u003e\\u003cstrong\\u003eA Pilot Case-Control Study of Obesity as a State of Metaflammation: Association with Toll-Like Receptor 2 (Arg753Gln) Gene Polymorphism\\u003c/strong\\u003e\\u003c/p\\u003e\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":true,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Inflammation, Leptin, Obesity, Target therapy, TLR2, TNF-α, Wnt5a\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-3310166/v2\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-3310166/v2\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003e Obesity is a worldwide health issue linked to chronic metabolic low-grade inflammation (metaflammation) causing multiple obesity-related comorbid conditions. Several mediators were related to this metaflammatory process.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eObjectives:\\u003c/strong\\u003e To assess the serum levels of leptin, wingless integration site family member 5A (Wnt5a), and tumor necrosis factor-alpha (TNF-α) as markers of obesity-associated metaflammation and investigate their association with toll-like receptors2 (TLR2) gene (Arg753Gln) single nucleotide polymorphism (SNP) among Egyptian females.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods: \\u003c/strong\\u003e\\u0026nbsp;This pilot case-control study included 60 females with obesity and 30 matched controls. Serum levels of leptin, Wnt5a, and TNF-α were assessed by ELISA, while TLR2 (Arg753Gln) genotyping was done by PCR-RFLP. The laboratory and anthropometric data of both groups were compared and correlated.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e Serum leptin, Wnt5a, and TNF-α showed significantly higher levels in females with obesity and a significant increase with higher classes of obesity. They showed positive correlations with each other and with body weight, body mass index, fat mass index, erythrocyte sedimentation rate, and waist and hip circumferences. Only TNF-α and Wnt5a were associated with metabolic syndrome (MetS) among the obesity group, with Wnt5a being the only independent risk factor for MetS. According to TLR2 (Arg753Gln) SNP, the homozygous GG genotype was associated with elevated levels of TNF-α, leptin, and Wnt5a compared to the heterozygous GA genotype, and it was associated with MetS among the obesity group. The frequencies of the heterozygous GA genotype and the A allele were higher among the obesity group without MetS than those with MetS.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion\\u003c/strong\\u003e:\\u003cstrong\\u003e \\u003c/strong\\u003eSerum leptin, Wnt5a, and TNF-α are significantly higher in women with obesity and the A allele of TLR2 (Arg753Gln) SNP is considered protective against MetS among them.\\u003c/p\\u003e\",\"manuscriptTitle\":\"A Pilot Case-Control Study of Obesity as a State of Metaflammation: Association with Toll-Like Receptor 2 (Arg753Gln) Gene Polymorphism\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":2,\"date\":\"2023-11-07 19:35:41\",\"doi\":\"10.21203/rs.3.rs-3310166/v2\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}},{\"code\":1,\"date\":\"2023-08-31 16:44:59\",\"doi\":\"10.21203/rs.3.rs-3310166/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"acf49836-bdf6-4411-8957-7a5bb5c7ec3a\",\"owner\":[],\"postedDate\":\"November 7th, 2023\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-01-22T14:28:12+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-3310166\",\"link\":\"https://doi.org/10.1038/s41598-025-85470-9\",\"journal\":{\"identity\":\"scientific-reports\",\"isVorOnly\":false,\"title\":\"Scientific Reports\"},\"publishedOn\":\"2025-01-21 00:00:00\",\"publishedOnDateReadable\":\"January 21st, 2025\"},\"versionCreatedAt\":\"2023-11-07 19:35:41\",\"video\":\"\",\"vorDoi\":\"10.1038/s41598-025-85470-9\",\"vorDoiUrl\":\"https://doi.org/10.1038/s41598-025-85470-9\",\"workflowStages\":[]},\"version\":\"v2\",\"identity\":\"rs-3310166\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-3310166\",\"identity\":\"rs-3310166\",\"version\":[\"v2\"]},\"buildId\":\"ApUGefWb6u5IBVtyqm6d5\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}