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Objective: : Investigate the prevalence of six specific Single Nucleotide Variants (SNVs) in IL-6 (rs2069845; rs1524107; rs2069832; rs2069849; rs2069840 and rs2069835) among individuals diagnosed with Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD), and Patent Ductus Arteriosus (PDA) and describe hematological parameters. Methods: Our study followed a cross-sectional model involving 76 newborns diagnosed with CHD between March 2022 and April 2023 at Fundação Hospital do Coração Francisca Mendes (FHCFM), a reference center of cardiology in Manaus city. Demographic and hematological data were collected consulting medical records. For DNA extraction, were utilized blood sample collected in FHCFM following QIAamp DNA Mini Kit (Qiagen) protocol. Was investigated six IL-6 Single Nucleotide Variants (SNVs) by quantitative Polymerase Chain Reaction (qPCR) using the TaqMan® SNP Genotyping Assay, set to rs2069845; rs1524107; rs2069832; rs2069849; rs2069840 and rs2069835 probes. All data were compiled and statistically analyzed by software Graphpad Prism 5.0 (Graphpad Software, San Diego, CA-USA) and IBM SPSS v.23 accordingly with each variable type, being considered statistically significant p-value < 0,05. Results: The rs2069849 mutant allele (T) were 3 times more prevalent in non-ASD when compared to ASD patients (p = 0,011; RR:0.296; 95%CI:0.089-0,797). The rs1524107 mutant allele (T) were 3,3 times more prevalent in the PDA (p < 0,001; RR:3.297; 95%CI:1.626-7.391). The opposite was observed to rs2069832 (p < 0,001; RR:0.219; 95%CI: 0,065-0,607). The rs2069845 mutant allele (A) were more likely to be present in complex CHD (p = 0,043; RR:1,37; 95%CI:0.985-2.249), while the rs2069832 mutant allele (A), were associated with simple CHD presentation (p < 0,001; RR:0.230; 95%CI:0.136-0.495). The presence of the rs1524107 mutant allele (T) were associated with PDA and presented higher frequencies in other CHD with PDA (p = 0.037). Patients with rs1524107 CC presented significant differences to hemoglobin (p = 0,019) and hematocrit (p = 0.042), the rs1524107 CT+TT genotype presented significate differences to white blood cells count (p = 0,044). Discussion: : It is described that interleukin-6 may contribute to increased risk to CHD through activation of inflammatory mechanisms which also could aggravate it physiological repercussions and response to prognostic evolution. Elevated expression of IL-6 has been associated with a hemostatic imbalance, pro-inflammatory, pro-atherogenic, and pro-thrombotic state, as well as an increased risk of cardiovascular events. IL-6 genotyping, we found a close relationship between rs1524107 mutant allele (T) presence and rs2069832 mutant allele (A) absent. Curiously, both rs1524107 and rs2069832 are associated with increased IL-6 levels and hematological repercussions. We hypothesize that collectively, these IL-6 SNVs haplotypes may balance and rule the inflammatory activation and modulate a physiological response through hematological repercussions which can result even to a major or minor aggravation of CHD. Conclusion: We found a strong correlation between rs1524107 with PDA. The rs1524107 is located at an important IL-6 regulatory region associated with increased IL-6 expression. We found lower WBC count in all PDA patients with rs1524107 CT/TT compared to rs1524107 CC genotype. We believe that our study may serve as an indicative to a more comprehensive approach with IL-6 SNVs and other inflammatory markers in CHD. |
