Variant rs17619600 in the gene encoding serotonin receptor 2B (HTR2B) increases the risk of gestational diabetes mellitus: a case–control study

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: This was a case–control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2Bwere genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM. 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: SNP rs17619600 in the HTR2Bgene influences glucose homeostasis, probably affecting insulin release, and the presence of the minor allele C was associated with a higher risk of GDM.