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RBP4 gene variants are associated with insulin resistance in women with previous gestational diabetes.

ABSTRACT: OBJECTIVE: This study aimed to examine possible genetic effects of some retinol binding protein-4 (RBP4) single nucleotide polymorphisms (SNPs) on the risk of gestational diabetes mellitus (GDM). In addition, the SNPs were examined for their possible association with insulin resistance at 6 weeks after delivery. METHODS: This was a prospective study of 100 women with GDM and 100 participants with normal gestation who were evaluated at gestational week 30 and 6 weeks postpartum. Three SNPs of RBP4 (rs3758539, rs116736522, and rs34571439) were genotyped using TaqMan assay. The genotype distributions between GDM patients and normal controls were analyzed using logistic regression models. In addition, differences in clinical characteristics among subjects grouped by genotype were assessed using the analysis of covariance test. RESULTS: The frequencies of the rare alleles were not significantly different between GDM patients and controls. However, we identified two variants rs3758539 and rs34571439 associated with insulin levels and insulin resistance in women with previous GDM. CONCLUSION: Noncoding SNPs of the RBP4 gene are not associated with GDM, but two SNPs showed associations with insulin resistance and insulin levels in women with prior GDM. Additional studies with increased sample size will be necessary in other GDM cohorts.

SUBMITTER: Saucedo R

PROVIDER: S-EPMC3934384 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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RBP4 gene variants are associated with insulin resistance in women with previous gestational diabetes.

Saucedo Renata R Zarate Arturo A Basurto Lourdes L Hernandez Marcelino M Puello Edgardo E Mendoza-Lorenzo Patricia P Ostrosky-Wegman Patricia P

Disease markers 20140209

<h4>Objective</h4>This study aimed to examine possible genetic effects of some retinol binding protein-4 (RBP4) single nucleotide polymorphisms (SNPs) on the risk of gestational diabetes mellitus (GDM). In addition, the SNPs were examined for their possible association with insulin resistance at 6 weeks after delivery.<h4>Methods</h4>This was a prospective study of 100 women with GDM and 100 participants with normal gestation who were evaluated at gestational week 30 and 6 weeks postpartum. Thre ...[more]

PMID: 24665145

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Project description:To investigate whether single nucleotide polymorphisms (SNPs) within 4 representative genes (VDR, GC, CYP2R1, and CYP24A1) encoding the core proteins involved in vitamin D production, degradation, and ligand-dependent signaling pathway are associated with gestational diabetes mellitus (GDM) in a Chinese population. A total of 1494 pregnant Han Chinese women (692 women with GDM and 802 women with normal glucose served as controls) were recruited through a 2-step approach. Participants were further divided into 2 groups according to body mass index before gestation (pre-BMI) (25?kg/m2). Nine SNPs (rs3733359, rs2282679, and rs16847024 in GC, rs2060793 and rs10741657 in CYP2R1, rs2248359 and rs6013897 in CYP24A1, rs11574143 and rs739837 in VDR) were genotyped using TaqMan allelic discrimination assays. The relationships between genotypes/alleles of a single locus as well as haplotypes of each gene and GDM were analyzed. We did not observe a significant difference in genotype frequency of each SNP between cases and controls. However, in the obese subgroup (pre-BMI ? 25 kg/m2), the risk allele-A of rs3733359 showed an association with increased risk of GDM (OR = 1.739, 95% CI = 1.066-2.837, P = 0.027). The GG-haplotype frequency of rs3733359 and rs2282679 in GC was modestly lower in the GDM group (OR = 0.848, 95% CI = 0.719-0.999, P = 0.048). Rs2060793 and rs10741657 were associated with insulin area under the curve (P = 0.028, P = 0.042, respectively), while rs739837 and rs6013897 demonstrated a correlation with fasting glucose (P = 0.019, P = 0.049, respectively). Additionally, rs2248359 displayed an association with leukocyte counts (B = 0.063 P = 0.033) and rs16847024 was related to high-sensitivity C-reactive protein levels (B = 0.086, P = 0.005). Our results indicate an association between GC variants and GDM, as well as a relation between a subset of loci in CYP2R1, CYP24A1, and VDR and clinical parameters related to GDM. Our findings may provide information for identifying biomarkers for early risk prediction of GDM and the pathways involved in disease progression.

Project description:BACKGROUND:A history of gestational diabetes mellitus (GDM) has been related to an elevated risk of type 2 diabetes. The melanocortin-4 receptor (MC4R) genotype has been related to glycemic changes in women with prior GDM. OBJECTIVE:The objective of this study was to analyze whether lifestyle intervention modified the association between the MC4R genotype and changes in insulin sensitivity among women with prior GDM. METHODS:We genotyped MC4R rs6567160 and measured glucose and insulin in fasting plasma samples at baseline and during the first 2 follow-up visits in 1128 women with prior GDM. They were randomly assigned to either a 4-y lifestyle intervention involving both diet and physical activity or a control group from a randomized clinical trial, the Tianjin Gestational Diabetes Mellitus Prevention Program. We analyzed the interaction between the MC4R genotype and lifestyle intervention on changes in insulin resistance. RESULTS:From baseline to 1.28 y, the MC4R genotype was related to changes in fasting insulin, HOMA-IR, and homeostasis model assessment of β cell function (HOMA-B) in the intervention group. Each risk allele (C) of rs6567160 was associated with a 0.08-unit greater decrease in log(insulin), log(HOMA-IR), and log(HOMA-B) (P = 0.02, 0.04, and 0.04, respectively), whereas in the control group, each C allele tended to be associated with a greater increase in HOMA-IR (P = 0.09). We found significant interactions between the MC4R genotype and lifestyle intervention on 1.28-y changes in fasting insulin and HOMA-IR (P = 0.006 and 0.008, respectively), and such interaction remained significant when we analyzed the trajectory of changes in insulin and HOMA-IR from baseline to 2.55 y (both P = 0.03). CONCLUSIONS:The exploratory results from the first 2 follow-up visits indicate that women with prior GDM carrying a diabetes-increasing MC4R genotype (CC or TC) may obtain better improvement than the TT genotype in insulin resistance through lifestyle intervention. This trial was registered at clinicaltrials.gov as NCT01554358.

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RBP4 gene variants are associated with insulin resistance in women with previous gestational diabetes.

Publications

RBP4 gene variants are associated with insulin resistance in women with previous gestational diabetes.

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