# Genetic Variants Associated with Life Expectancy in Patients with Chagas Disease

## TL;DR

This study identifies genetic variants linked to survival in Chagas disease patients, which could help identify high-risk individuals.

## Contribution

The study identifies specific SNPs associated with survival in Chagas disease patients, offering potential for personalized risk assessment.

## Key findings

- Variant rs3755863 (PPARGC1A gene) is associated with increased risk of death.
- Variants rs7310615 (SH2B3 gene) and rs7405731 (JUP gene) show protective effects against mortality.
- A genetic risk score was developed to estimate survival based on SNP profiles.

## Abstract

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 >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 < 0.05 were selected to construct a risk score, which was then assessed using Kaplan–Meier 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: 3.4–6.5). 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–Meier 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.