{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:11:37Z","timestamp":1792066297636,"version":"4.4.0"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01NS110100"],"award-info":[{"award-number":["R01NS110100"]}]},{"name":"NIH","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}]},{"name":"NIH","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}]},{"name":"MIND Institute Intellectual and Developmental Disabilities Research Center","award":["R01NS110100"],"award-info":[{"award-number":["R01NS110100"]}]},{"name":"MIND Institute Intellectual and Developmental Disabilities Research Center","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}]},{"name":"MIND Institute Intellectual and Developmental Disabilities Research Center","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this study, the potential role and interaction of the APO\u03b5 and KLOTHO genes on the penetrance of fragile X-associated tremor\/ataxia syndrome (FXTAS) and on the IQ trajectory were investigated. FXTAS was diagnosed based on molecular, clinical and radiological criteria. Males with the premutation (PM) over 50 years, 165 with and 34 without an FXTAS diagnosis, were included in this study and were compared based on their APO (\u03b52-\u03b53-\u03b54) and KLOTHO variant (KL-VS) genotypes. The effect of APO\u03b54 on FXTAS stage and on diagnosis did not differ significantly by KL-VS genotype with interaction effect p = 0.662 and p = 0.91, respectively. In the FXTAS individuals with an APO\u03b52 allele, a marginal significance was observed towards a larger decline in verbal IQ (VIQ) in individuals with an APO\u03b54 allele compared to those without an APO\u03b54 allele (p = 0.071). In conclusion, our findings suggest that the APO\u03b54 and KL-VS genotypes alone or through their interaction effect do not appear to predispose to either FXTAS diagnosis or stage in male carriers of the PM allele. A further study is needed to establish the trend of IQ decline in the FXTAS individuals who carry APO\u03b54 with APO\u03b52 compared to those without APO\u03b54.<\/jats:p>","DOI":"10.3390\/ijms25158103","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T08:40:04Z","timestamp":1721896804000},"page":"8103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor\/Ataxia Syndrome"],"prefix":"10.3390","volume":"25","author":[{"given":"Tri Indah","family":"Winarni","sequence":"first","affiliation":[{"name":"Center for Biomedical Research (CEBIOR), Faculty of Medicine, Universitas Diponegoro, Semarang 50275, Central Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Hyun","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Marlyand, College Park, MD 20742, USA"},{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3460-9805","authenticated-orcid":false,"given":"David","family":"Hessl","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blythe P.","family":"Durbin-Johnson","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Medicine, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5965-1981","authenticated-orcid":false,"given":"Agustini","family":"Utari","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research (CEBIOR), Faculty of Medicine, Universitas Diponegoro, Semarang 50275, Central Java, Indonesia"},{"name":"Department of Pediatrics, Faculty of Medicine, Universitas Diponegoro, Semarang 50275, Central Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-8448","authenticated-orcid":false,"given":"Randi","family":"Hagerman","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-9180","authenticated-orcid":false,"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA"},{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tassone, F., Protic, D., Allen, E.G., Archibald, A.D., Baud, A., Brown, T.W., Budimirovic, D.B., Cohen, J., Dufour, B., and Eiges, R. 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