{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:20:01Z","timestamp":1773674401062,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novartis Argentina"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Single nucleotide polymorphisms (SNPs), as common genetic variations, can influence biological processes. Identifying these variations is crucial for recognizing high-risk subgroups, guiding preventive strategies, and enabling personalized management. Objective: This study aimed to determine the relationship between SNPs and survival, thereby identifying genetic profiles associated with increased risk. Methods: We included seropositive patients with Chagas disease who had a disease duration of &gt;20 years and no comorbidities. DNA was extracted. A SNP panel focusing on genes involved in cardiac structure was created from the GnomAD database. Patients were followed for 8 years to assess survival. The association between SNPs and survival was evaluated, and a genetic risk score was generated. Univariate and multivariate Cox regression models assessed the association between SNPs (coded as ordinal variables) and survival time. SNPs with p &lt; 0.05 were selected to construct a risk score, which was then assessed using Kaplan\u2013Meier curves and median survival times. Results: A total of 182 patients were included, with 96.7% completing follow-up for a median of 5.1 years (interquartile range: 3.4\u20136.5). The median age was 62 years; 39.6% of patients were male, and 31% had reduced left ventricular ejection fraction. Univariate analysis showed that 3 of the 68 SNPs studied were associated with survival. Variant rs3755863 (PPARGC1A gene) was significantly associated with an increased risk of death (hazard ratio, HR = 1.94; p = 0.022). Conversely, two variants, rs7310615 (SH2B3 gene) and rs7405731 (JUP gene), showed a protective effect with significantly reduced mortality risk (HR = 0.45; p = 0.006 and HR = 0.48; p = 0.006, respectively). In multivariate analysis, rs7310615 and rs7405731 remained significantly associated with survival. A genetic risk score was constructed, assigning 0 points for homozygous wild-type, 1 point for heterozygotes, and 2 points for homozygous alternative alleles. Individual scores were calculated, and survival was estimated for each score category using Kaplan\u2013Meier analysis and median survival times. Conclusions: Two SNPs were identified as significantly associated with survival. These findings require confirmation in larger and more diverse populations. Their validation could enable the identification of a subgroup of patients at particularly high risk.<\/jats:p>","DOI":"10.3390\/medsci14010137","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:32:07Z","timestamp":1773667927000},"page":"137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variants Associated with Life Expectancy in Patients with Chagas Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Mario Bruno","family":"Principato","sequence":"first","affiliation":[{"name":"Cardiology Department, Ramos Mej\u00eda Hospital, Ciudad Aut\u00f3noma de Buenos Aires C1221ADC, Argentina"},{"name":"Argentine Society of Cardiology, Ciudad Aut\u00f3noma de Buenos Aires C1115AAD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Victoria","family":"Carvelli","sequence":"additional","affiliation":[{"name":"Cardiology Department, Ramos Mej\u00eda Hospital, Ciudad Aut\u00f3noma de Buenos Aires C1221ADC, Argentina"},{"name":"Argentine Society of Cardiology, Ciudad Aut\u00f3noma de Buenos Aires C1115AAD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Analia","family":"Paolucci","sequence":"additional","affiliation":[{"name":"Cardiology Department, Ramos Mej\u00eda Hospital, Ciudad Aut\u00f3noma de Buenos Aires C1221ADC, Argentina"},{"name":"Argentine Society of Cardiology, Ciudad Aut\u00f3noma de Buenos Aires C1115AAD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Principato","sequence":"additional","affiliation":[{"name":"Cardiology Department, Facultad de Medicina, Universidad del Salvador, Ciudad Aut\u00f3noma de Buenos Aires C1023AAB, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocio","family":"Villa Fernandez","sequence":"additional","affiliation":[{"name":"Cardiology Department, Ramos Mej\u00eda Hospital, Ciudad Aut\u00f3noma de Buenos Aires C1221ADC, Argentina"},{"name":"Argentine Society of Cardiology, Ciudad Aut\u00f3noma de Buenos Aires C1115AAD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Gempre, Genomics and Precision Preventive Medicine, Ciudad Aut\u00f3noma de Buenos Aires C1087ACQ, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Ercoli","sequence":"additional","affiliation":[{"name":"Gempre, Genomics and Precision Preventive Medicine, Ciudad Aut\u00f3noma de Buenos Aires C1087ACQ, Argentina"},{"name":"Biotech Genetic Solutions\u2014Oncological Genetics, Ciudad Aut\u00f3noma de Buenos Aires C1048AAJ, Argentina"},{"name":"Preventive Genetics Department, Austral University Hospital, Pilar B1629AHJ, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4334-6741","authenticated-orcid":false,"given":"Guillermo Alberto","family":"Keller","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Medicina, Ciudad de Buenos Aires C1121ABG, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Di Girolamo","sequence":"additional","affiliation":[{"name":"Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional, Universidad de Buenos Aires, Ciudad Aut\u00f3noma de Buenos Aires C1122AAJ, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Lago","sequence":"additional","affiliation":[{"name":"Cardiology Department, Ramos Mej\u00eda Hospital, Ciudad Aut\u00f3noma de Buenos Aires C1221ADC, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justo","family":"Carbajales","sequence":"additional","affiliation":[{"name":"Cardiology Department, Ramos Mej\u00eda Hospital, Ciudad Aut\u00f3noma de Buenos Aires C1221ADC, Argentina"},{"name":"Argentine Society of Cardiology, Ciudad Aut\u00f3noma de Buenos Aires C1115AAD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, February 14). 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