Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus

Abstract

BackgroundsTwo SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM) in previous studies. Since T2DM and gestational diabetes mellitus (GDM) share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes.MethodsA total of 1,918 subjects (928 GDM patients and 990 controls) were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs), 95% confidence intervals (CIs), and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed.ResultsWe found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses.ConclusionThere have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.

Genetic variants and the risk of gestational diabetes mellitus: a systematic review

“…A meta-analysis of these studies showed that the T allele of rs4402960 was significantly associated with an increased risk of GDM [pooled OR 1.21 (95% CI 1.10 -1.33), P , 0.001; Table IV Melatonin receptor 1B (MTNR1B) Kim et al (2011) first found a significant association of GDM risk with two variants in the MTNR1B locus, rs10830963 and rs1387153, which are in tight linkage disequilibrium (LD) with each other (|D…”

Identification of trends in scientific publications related to genetic polymorphisms in gestational diabetes mellitus

“…Additionally, polymorphisms in the MTNR1B gene were associated with increased risk of DM2. Moreover, an association was observed between the rs10830963 polymorphism and GDM in different populations; however, this must be further validated in other populations (Kim et al, 2011).…”

Melatonin Receptor 1B Gene Polymorphisms, Haplotypes and Susceptibility to Schizophrenia

“…These two SNPs were investigated with various diseases such as systemic lupus erythematous (SLE) (21), breast cancer (22), polycystic ovary especially (23), type II diabetes (24), and gestational diabetes (6,25). Tanev investigated the impact of MTN1B rs1562444, rs10830962, and rs10830963 polymorphisms on SLE on 109 SLE females and 101 healthy women; they found that CC genotype of rs10830963 polymorphism significantly increased the risk of SLE when compared with CG and GG genotypes (21).…”

“…Melatonin, also known as N-acetyl 1-5-methnxytryptamine, is a neuro hormone synthesized and secreted by the pineal gland of the mammalian brain to regulate the circadian rhythm, and affects other physiological functions with peaks during night time (6). This hormone for beginning its performance must interact with receptors, MT1 (Mel 1a encoded by MTNR1A) and MT2 (Mel 1b , encoded by MTNR1B), which are two membrane receptors isoforms to transmit the action and effects of melatonin by G-protein coupled 7-transmembrane receptors mechanism.…”