Variant rs17619600 in the gene encoding serotonin receptor 2B (HTR2B) increases the risk of gestational diabetes mellitus: a case-control study.
Beta cell
HTR2B
Serotonin
Single nucleotide polymorphisms
Journal
European journal of medical research
ISSN: 2047-783X
Titre abrégé: Eur J Med Res
Pays: England
ID NLM: 9517857
Informations de publication
Date de publication:
21 Jul 2023
21 Jul 2023
Historique:
received:
13
10
2022
accepted:
05
07
2023
medline:
24
7
2023
pubmed:
22
7
2023
entrez:
21
7
2023
Statut:
epublish
Résumé
During pregnancy, the increase in maternal insulin resistance is compensated by hyperplasia and increased function of maternal pancreatic beta cells; the failure of this compensatory mechanism is associated with gestational diabetes mellitus (GDM). Serotonin participates in beta cell adaptation, acting downstream of the prolactin pathway; the blocking of serotonin receptor B (HTR2B) signaling in pregnant mice impaired beta cell expansion and caused glucose intolerance. Thus, given the importance of the serotoninergic system for the adaptation of beta cells to the increased insulin demand during pregnancy, we hypothesized that genetic variants (single nucleotide polymorphisms [SNPs]) in the gene encoding HTR2B could influence the risk of developing GDM. This was a case-control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2B were genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM. Only the minor allele C of SNP rs17619600 conferred an increased risk for GDM in the codominant model (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.53-3.09; P < 0.0001) and in the rare dominant model (OR 2.32; CI 1.61-3.37; P < 0.0001). No associations were found between the SNPs and insulin use, maternal weight gain, newborn weight, or the result of postpartum oral glucose tolerance test (OGTT). In the overall population, carriers of the XC genotype (rare dominant model) presented a higher area under the curve (AUC) of plasma glucose during the OGTT, performed for diagnostic purposes, compared with carriers of the TT genotype of rs17619600. SNP rs17619600 in the HTR2B gene influences glucose homeostasis, probably affecting insulin release, and the presence of the minor allele C was associated with a higher risk of GDM.
Sections du résumé
BACKGROUND
BACKGROUND
During pregnancy, the increase in maternal insulin resistance is compensated by hyperplasia and increased function of maternal pancreatic beta cells; the failure of this compensatory mechanism is associated with gestational diabetes mellitus (GDM). Serotonin participates in beta cell adaptation, acting downstream of the prolactin pathway; the blocking of serotonin receptor B (HTR2B) signaling in pregnant mice impaired beta cell expansion and caused glucose intolerance. Thus, given the importance of the serotoninergic system for the adaptation of beta cells to the increased insulin demand during pregnancy, we hypothesized that genetic variants (single nucleotide polymorphisms [SNPs]) in the gene encoding HTR2B could influence the risk of developing GDM.
METHODS
METHODS
This was a case-control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2B were genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM.
RESULTS
RESULTS
Only the minor allele C of SNP rs17619600 conferred an increased risk for GDM in the codominant model (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.53-3.09; P < 0.0001) and in the rare dominant model (OR 2.32; CI 1.61-3.37; P < 0.0001). No associations were found between the SNPs and insulin use, maternal weight gain, newborn weight, or the result of postpartum oral glucose tolerance test (OGTT). In the overall population, carriers of the XC genotype (rare dominant model) presented a higher area under the curve (AUC) of plasma glucose during the OGTT, performed for diagnostic purposes, compared with carriers of the TT genotype of rs17619600.
CONCLUSIONS
CONCLUSIONS
SNP rs17619600 in the HTR2B gene influences glucose homeostasis, probably affecting insulin release, and the presence of the minor allele C was associated with a higher risk of GDM.
Identifiants
pubmed: 37480094
doi: 10.1186/s40001-023-01211-6
pii: 10.1186/s40001-023-01211-6
pmc: PMC10362639
doi:
Substances chimiques
Insulin
0
Receptor, Serotonin, 5-HT2B
0
HTR2B protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
243Informations de copyright
© 2023. The Author(s).
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