Genetic Contribution of the Adrenergic, Cholinergic, and Serotonergic Systems to Leiomyoma Development and Treatment.
Int J Mol Cell Med
; 12(4): 320-334, 2023.
Article
in En
| MEDLINE
| ID: mdl-39006196
ABSTRACT
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_000024.6c.46G>A, NP_000015.2p. Gly16Arg), cholinergic (CHRNA5 - rs16969968, NM_000745.3c.1192G>A, NP_000736.2p.Asp398Asn), and serotonergic systems (SLC6A4 - 5-HTTVNTR-intron2, HTR2A - rs6313, NM_000621.5c.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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Int J Mol Cell Med
Year:
2023
Document type:
Article
Affiliation country:
Portugal