{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:46:10Z","timestamp":1790660770988,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p &lt; 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: \u22120.6 [(\u22120.89)\u2013(\u22120.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08\u20130.16]; FGF23 MD [95% CI]: 12.8 [5.9\u201319.6]; PTX3 MD [95% CI]: 13.3 [8.9\u201317.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype\u2013phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.<\/jats:p>","DOI":"10.3390\/life12050631","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T21:16:28Z","timestamp":1650921388000},"page":"631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of Surrogate Markers for Cardiovascular Disease in Familial Mediterranean Fever-Related Amyloidosis Patients Homozygous for M694V Mutation in MEFV Gene"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5365-3457","authenticated-orcid":false,"given":"Sezgin","family":"Sahin","sequence":"first","affiliation":[{"name":"Department of Paediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Romano","sequence":"additional","affiliation":[{"name":"Division of Paediatric Rheumatology, Department of Paediatrics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Canadian Behcet and Autoinflammatory Disease Center (CAN-BE-AID), University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferhat","family":"Guzel","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratories, Genetics Research and Genome Center, Department of Research and Development, Ant Biotechnology, Istanbul 34775, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Piskin","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute, London Health Sciences Center, London, ON N6C 2R5, Canada"},{"name":"Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-9334","authenticated-orcid":false,"given":"Dimitri","family":"Poddighe","sequence":"additional","affiliation":[{"name":"Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan"},{"name":"Clinical Academic Department of Pediatrics, National Research Center of Maternal and Child Health, University Medical Center, Nur-Sultan 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siren","family":"Sezer","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Atilim University Faculty of Medicine, Ankara 06830, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-7720","authenticated-orcid":false,"given":"Ozgur","family":"Kasapcopur","sequence":"additional","affiliation":[{"name":"Department of Paediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7148-0767","authenticated-orcid":false,"given":"C.","family":"Appleton","sequence":"additional","affiliation":[{"name":"Canadian Behcet and Autoinflammatory Disease Center (CAN-BE-AID), University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Lawson Health Research Institute, London Health Sciences Center, London, ON N6C 2R5, Canada"},{"name":"Division of Rheumatology, Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilker","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Epigenetic Health Solutions, Unit of Nephrology, Ankara 06810, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkan","family":"Demirkaya","sequence":"additional","affiliation":[{"name":"Division of Paediatric Rheumatology, Department of Paediatrics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Canadian Behcet and Autoinflammatory Disease Center (CAN-BE-AID), University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Lawson Health Research Institute, London Health Sciences Center, London, ON N6C 2R5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/S0140-6736(06)68430-4","article-title":"Familial mediterranean fever in Arabs","volume":"367","author":"Majeed","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/j.1469-1809.2008.00471.x","article-title":"The population genetics of familial mediterranean fever: A meta-analysis study","volume":"72","author":"Papadopoulos","year":"2008","journal-title":"Ann. 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