Association Between a Melatonin Receptor IB Genetic Polymorphism and Its Protein Expression in Gestational Diabetes Mell
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Association Between a Melatonin Receptor 1B Genetic Polymorphism and Its Protein Expression in Gestational Diabetes Mellitus
Reproductive Sciences 1-7 ยช The Author(s) 2018 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1933719118765983 journals.sagepub.com/home/rsx
Chao Li, PhD1, Yubin Zhou, MD2, Binglong Qiao, MD3, Lin Xu, PhD3, Yan Li, MD3, and Can Li, MD1
Abstract Aims: This study was conducted to investigate the relationship between a genetic polymorphism and the expression of melatonin receptor 1B (MTNR1B) in the placenta of Han Chinese women with gestational diabetes mellitus (GDM). Methods: In this study, 215 patients with GDM and 243 healthy controls were genotyped using direct sequencing for the MTNR1B single-nucleotide polymorphism rs10830963. The expression of MTNR1B in placenta was detected by immunohistochemistry and Western blotting. The association of rs10830963 with the expression of MTNR1B, plasma glucose, and insulin levels as well as blood lipid levels was investigated. Results: The genotype and allele frequencies of rs10830963 were significantly different between women with GDM and controls (P < .05). Fasting blood glucose, fasting insulin, and homeostasis model assessment for insulin resistance in women with GDM with the GG and GC genotypes were significantly higher than those with the CC genotype (P < .05). The expression level of MTNR1B in placenta was significantly higher in the GDM group than in the control group (P < .05). The expression of MTNR1B was significantly higher in all participants with the GG and GC genotypes (1.31 [0.74]) than in pregnant women with the CC genotype (0.92 [0.52], P < .05). Conclusions: The genetic polymorphism rs10830963 in MTNR1B and its protein expression levels in placenta are associated with an increased risk of developing GDM. Furthermore, rs10830963 may tag a molecular mechanism leading to insulin resistance in Han Chinese women with GDM. Keywords polymorphisms, single nucleotide, diabetes, gestational, insulin resistance, MTNR1B
Introduction Gestational diabetes mellitus (GDM) is a common obstetric complication and is defined as glucose intolerance first diagnosed during pregnancy.1 Approximately 5% to 10% of Asian pregnant women have GDM, and the prevalence of GDM is continually rising in China.2 Gestational diabetes mellitus is associated with short- and long-term complications for both mothers and offspring.3 The pathogenesis of GDM is not clear but is generally recognized as a combination of genetic and environmental risk factors.4 As GDM and type 2 diabetes mellitus (T2DM) share similarities in their pathogenesis with respect to impaired insulin secretion and increased insulin resistance,5 it is possible that GDM is a multigenic disease related to T2DM. Melatonin receptor 1B (MTNR1B), which belongs to a class of G-protein-coupled receptors, has recently attracted considerable attention as a novel candidate gene contributing to T2DM.6 MTNR1B has been reported to be associated with T2DM in various ethnic groups. 7-9 Sever
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