Análise de polimorfismos nos genes CATALASE, SOD2, NOS3, TGFß e GSTP no surto de rabdomiólise no interior do estado do Amazonas

Abstract

Rhabdomyolysis, a condition characterized by the breakdown of muscle cells, frequently manifests through symptoms such as myalgia, muscle weakness, myoglobinuria, and severe renal injury. The primary causes include physical trauma, intense physical activity, exposure to toxins or drugs, as well as metabolic or genetic disorders. A recent outbreak was reported in the state of Amazonas, with the Fundação de Vigilância Sanitária – FVS RCP/AM confirming 103 cases by january 2022 to january 2023, of which 67 (65%) occurred in the municipality of Itacoatiara alone. The primary objective of this study was to determine the prevalence of genetic polymorphisms in CATALASE, SOD3, NOS3, TGFβ, and GST, with the aim of identifying potential molecular markers of susceptibility or protection associated with rhabdomyolysis. Clinical and epidemiological data collection was conducted through interviews and the analysis of medical records, focusing on events related to symptom onset. For molecular analyses, genomic DNA was extracted using the QIAamp DNA Mini Kit (Qiagen) method, followed by polymorphism determination through real-time PCR (qPCR) using the QuantStudio 6 equipment. Clinical, epidemiological, and molecular data were compiled into databases and analyzed using GraphPad Prism 5.0 and SPSS v.19 software, according to the nature of the variables. Statistical analyses for categorical variables in multiple groups were conducted using the Chi-square test (χ2), with appropriate corrections applied using Mantel-Haenszel and Yates tests. This study analyzed 146 patients with rhabdomyolysis, predominantly men (54.1%), with an average age of 47.7 years for men and 50.7 years for women. Most patients (51.7%) resided in Itacoatiara, Amazonas, with limited access to specialized care. The most common clinical manifestations included myalgia (56.4%), nausea (20.5%), and lumbar pain (15.2%), with symptoms being more frequent among women. Hematological and biochemical analyses revealed that men presented lower hematological indices and elevated markers of hemolysis, suggesting greater disease severity. Notably, men exhibited significantly higher AST levels, reflecting more severe muscle injuries. Elevated CK-MB levels also indicated potential cardiac complications. Genetic analysis identified polymorphisms associated with greater susceptibility to severe clinical manifestations. In particular, the -262CC genotype of catalase was significantly associated with a higher risk (RR: 4.4) of abdominal pain, likely due to reduced detoxification capacity and increased oxidative stress. These findings underscore the interaction between environmental, clinical, and genetic factors in the progression of rhabdomyolysis in the Amazon region.