Association between the rs4753426 polymorphism in MTNR1B with fasting plasma glucose level and pancreatic β-cell function in gestational diabetes mellitus

Abstract

ABSTRACT. We investigated the association between rs4753426 single nucleotide polymorphisms in the melatonin receptor 1B (MTNR1B) gene and the risk of developing gestational diabetes mellitus (GDM). A total of 516 gravidas (186 with GDM and 330 non-diabetic controls) were enrolled in the study. Genotype and allele frequencies of rs4753426 in the MTNR1B gene were detected by DNA sequencing. Fasting plasma glucose and fasting insulin levels were measured to calculate the homeostasis model assessment for insulin resistance (HOMA-IR) and for b-cell function. Three genotypes (CC, CT, and TT) were found in both groups. The frequencies of CC, CT, and TT genotypes for the GDM group were 70.97, 22.58, and 6.45% vs 53.03, 39.70, and 7.27% in the control group, respectively. Significant differences were observed in genotype frequencies between groups (P < 0.05). T and C allele frequencies in the GDM group were 17.74 and 82.26%, respectively, and in the control group were 27.12 and 72.88%, respectively. Significant differences in T and C allele frequencies were found between groups (P < 0.05). In the GDM group, the C allele was associated with increased fasting plasma glucose level and reduced pancreatic b-cell function (P < 0.05). There were no significant differences in total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein concentration, or HOMA-IR between groups (P > 0.05). The single nucleotide polymorphism rs4753426 in MTNR1B may be a susceptibility gene locus for GDM, and the C allele may contribute to the increased fasting plasma glucose level and reduced pancreatic b-cell function.

MTNR1B genetic polymorphisms as risk factors for gestational diabetes mellitus: a case-control study in a single tertiary care center

“…Previous case-control and meta-analysis studies and GWAS on global ethnically diverse populations have confirmed that the rs10830963 and rs1387153 variants in MTNR1B are positively associated with GDM as major risk factors. 14,15,19,23,25-28,46-51 A recent study confirmed that the G allele of rs10830963 is strongly associated with glycemic traits in GDM. 47 In addition the MTNR1B rs10830963 variant, in interaction with prepregnancy BMI, was reported as a predictive genetic marker for the need of antenatal insulin therapy in GDM.…”

“…The human genome project discovered MTNR1B gene SNPs, including rs1387153 (chr11:92940662) and rs10830963 (chr11:92975544), that were associated with an increased risk of diabetes development. 19 The prevalence of GDM in Saudi women is 18.7%, 20 and the major factors contributing to the risk of GDM in this population are a lack of exercise and poor dietary control; the prevalence of obesity in Saudi Arabia is documented at 68%. 1 According to a recent meta-analysis, 14,15 no studies on the MTNR1B gene have been conducted in Saudi populations, or in other Arab/Middle Eastern populations.…”

Association Between a Melatonin Receptor IB Genetic Polymorphism and Its Protein Expression in Gestational Diabetes Mellitus

“…However, these changes worsen insulin resistance in pregnant women with GDM. 27 Any alteration in placental development or function may contribute to insulin resistance; therefore, the placenta is a good model to study changes in metabolic programming in women with GDM.…”

Gestational Diabetes Mellitus: The Genetic Susceptibility Behind the Disease

“…Melatonin receptor 1B (MTNR1B) is located on human chromosome 11q14.3 and encodes MT2, one of the 2 high-affinity forms of the melatonin receptor [30,31]. MTNR1B is principally expressed in the retina, brain, and pancreatic cells; and is involved in the regulation of insulin release, circadian rhythms, and blood glucose homeostasis by modifying the melatonin-signaling pathway [32]. A recent meta-analysis that included the MTNR1B rs1387153, rs4753426, and rs10830963 loci in a case-control study with 23 participants of Caucasians origin and individuals in Asia and Mexico, findings indicated that the rs1387153, rs4753426, and rs10830963 polymorphisms were associated with a widely regional susceptibility to GDM [33].…”