Departamento Biomédico
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Examinando Departamento Biomédico por Autor "Alexis M. Kalergis"
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Ítem Characterization of LDLR rs5925 and PCSK9 rs505151 genetic variants frequencies in healthy subjects from northern Chile: Influence on plasma lipid levels(2019) Claudio Rojas; Hugo Ramírez; Luis A. Salazar; Alexis M. Kalergis; Anita S. Gálvez; Jorge Escobar‐VeraBackground: Identification and characterization of genetic variants and their effects on human health may allow to establish relationships between genetic background and susceptibility to developing cardiovascular diseases. LDLR and PCSK9 polymorphisms have been associated with higher lipid levels and risk of cardiovascular diseases. Thus, the main aim of this study was to evaluate genotype distribution and relative allelic frequency of LDLR rs5925 (1959C > T) and PCSK9 rs505151 (23968 A > G) genetic variants and their effects on lipid levels of healthy subjects from northern Chile. Methods: A total of 178 healthy individuals were recruited for this study. The genotyping of rs5925 (LDLR) and rs505151 (PCSK9) polymorphisms was performed by PCR‐RFLP and qPCR, respectively. In addition, glucose and lipid levels were determined and associated with the genetic data. Results: Genotype distribution for LDLR rs5925 polymorphism was as follows: CC = 19%; CT = 53%; and TT = 28% (HWE: χ2 = 0.80; P = .37), and for PCSK9 rs505151 genetic variant was as follows: AA = 93%; AG = 7%; and GG = 0% (HWE: χ2 = 0.22; P = .64). The frequency of T (rs5925) and G (rs505151) mutated alleles was 0.55 and 0.03, respectively. Data showed that individuals carrying LDLR mutated allele (T) presented lower values of total cholesterol, triglycerides, and LDL‐cholesterol when compared to CC homozygous genotype (P < .05). Subgroup analysis revealed that women carrying the PCSK9 mutated allele (G) exhibited higher values of total cholesterol, triglycerides, HDL‐C, and LDL‐C when compared to male group carrying the same genotype (P<05). Conclusions: The effect of LDLR rs5925 and PCSK9 rs505151 gene polymorphisms on lipid levels is associated with gender among healthy subjects from northern Chile.Ítem Contribution of Fcy Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus(2019) Orlando A. Acevedo; Fabián E. Díaz; Tomas E. Beals; Felipe M. Benavente; Jorge A. Soto Pablo A. González Alexis M. Kalergis; Jorge Escobar Vera; Pablo A. González; Alexis M. KalergisThe human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways