Abstract Body (Do not enter title and authors here): Background: Chagas disease (CD) is an infectious disease caused by the protozoa Trypanosoma cruzi, affecting around 6-7 million people in Latin America. Although most infected individuals remain asymptomatic throughout their lives, annually 2-5% of them progress to chronic chagasic cardiomyopathy (CCC), digestive megasyndromes, or both. Ficolins are innate immunity proteins that play a crucial role in the lectin pathway (LP) of complement activation. They recognize pathogen-associated molecular patterns and mediate the clearance of apoptotic cells and cellular debris. Genetic polymorphisms of components of LP have been associated with clinical forms of CD; however, the relationship between Ficolin-1 (FCN1) gene polymorphisms and CD remains unclear. Hypothesis: We hypothesize that polymorphisms in the FCN1 gene, previously related to its expression, are associated with clinical forms of CD, possibly impacting LP activation. Goals: To investigate the association of genetic variants of the FCN1 gene with the clinical forms of chronic CD. Methods: We evaluated three single-nucleotide polymorphisms (SNPs): rs2989727G>A (c.-1981G>A), rs17039495 (-399G>A) and rs10858293 (+33G>T) by sequence-specific amplification in 200 patients with chronic CD (23.5% asymptomatic, 52% CCC, 10% digestive form, and 14.5% cardiodigestive form) from Southern Brazil, and 210 T. cruzi seronegative controls. Logistic regression models were adjusted for sex, age, and self-identified ethnicity, followed by Bonferroni correction. Results: The haplotypes GGG, AGT, AGG, GAT, and AAT were more frequently found in patients, while GGG, AGT, AGG, and AAT were more common in controls. We observed a higher frequency of the G allele (p=0.004; OR 1.49; 95% CI 1.14, 1.99) of SNP rs2989727 and the GG genotype (p=0.010; OR 1.82; 95% CI 1.10, 3.03) in CD patients, particularly those with symptomatic forms (p=0.008; OR 1.51; 95% CI 1.11, 2.03; and p=0.012; OR 2.05; 95% CI 1.17, 3.59) and CCC (p=0.013; OR 1.54; 95% CI 1.10, 2.16, and p=0.013; OR 2.16; 95% CI 1.18, 3.97), compared to the control group. Conclusion: The FCN1 rs2989727 variant is associated with chronic CD and CCC, likely due to its impact on FCN1 gene expression.