Autor(es): Inácio, Ângel ; Aguiar, Laura ; Carrilho, Raquel ; Pires, Patrícia ; Ferreira, Joana ; Coelho, Luís ; Mascarenhas, Mário Rui ; Sardinha, Luís ; Bilhim, Tiago ; Pisco, João ; Bicho, Manuel ; Bicho, Maria Clara
Data: 2023
Identificador Persistente: http://hdl.handle.net/10362/175363
Origem: Repositório Institucional da UNL
Assunto(s): ADBR2; CHRNA5; embolization; HTR2A; Leiomyomas; SLC6A4; Biotechnology; Biochemistry; Molecular Medicine; Molecular Biology; Genetics; Cell Biology
Funding Information: study, we conclude that the ADBR2 and CHRNA5 genes have a relevant role in the development of leiomyoma. This role appears to be enhanced by the epistatic relationship with the genes HTR2A and SLC6A4. This study, confirms the involvement of the Autonomous Nervous System in tumor biology, along with the genetics of the mechanisms, involved in chronic stress. By highlighting and helping to elucidate the role of genes involved in the pathophysiology of leiomyoma disease and leiomyoma treatment, we believe that this research paves the way for the investigation of new therapies that interfere with the neurotransmitter systems of the nervous system and is a promising step forward in personalized medicine, by indicating individual susceptibility to the disease. Acknowledgments We would like to thank the Instituto de Investiga\u00E7\u00E3o Cient\u00EDfica Bento da Rocha Cabral for financial support. We thank all of the participants who contributed in the study. We dedicate this work to the memoriam of Professor Pisco. References Publisher Copyright: © The Author(s).
The link between the autonomic nervous system and tumor biology is being unfold. We aim to study the contribution of genes of the adrenergic (ADBR2 - rs1042713, NM_000024.6:c.46G>A, NP_000015.2:p. Gly16Arg), cholinergic (CHRNA5 - rs16969968, NM_000745.3:c.1192G>A, NP_000736.2:p.Asp398Asn), and serotonergic systems (SLC6A4 - 5-HTTVNTR-intron2, HTR2A - rs6313, NM_000621.5:c.102C>T, NP_001365853.1: p. Ser 34=) to gynecological tumorigenesis and their treatment by embolization. A total of 517 DNA samples from women were analyzed. Samples were genotyped by PCR, PCR-RFLP and EndPoint genotyping. Results show a statistically significant association between the AA genotype of the ADBR2 gene and GG genotype of the CHRNA5 gene with leiomyoma (OR = 2.311; p = 0.003 and OR = 2.165; p = 0.001, respectively), and the epistatic interaction between genotypes increases the risk (OR = 2.458; p= 0.043). The GG genotype (CHRNA5) shows a lower reduction of the volume of the main leiomyoma after treatment (p=0.015). Combination of the genotypes 12/12-AA (SLC6A4 - ADBR2) increases the risk to leiomyoma (OR = 2.540, p= 0.030). TT genotype of HTR2A gene in combination with any of the two risk genotypes (of ADBR2 or CHRNA5) increases substantially the risk (OR = 5.266, p = 0.006; OR = 6.364, p=0.007, respectively). We conclude that ADBR2 and CHRNA5 genes have a relevant role that is enhanced by the epistatic relationship with the genes HTR2A and SLC6A4. CHRNA5 gene may also be a modulator of the success of embolization. We confirm the contribution of the genetics of Autonomous Nervous System to tumor biology.
