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褪黑素受体 1B 基因多态性及其蛋白表达与妊娠期糖尿病的关系。

Association Between a Melatonin Receptor 1B Genetic Polymorphism and Its Protein Expression in Gestational Diabetes Mellitus.

机构信息

Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China.

Department of medicine, Qingdao University, Qingdao, China.

出版信息

Reprod Sci. 2019 Oct;26(10):1382-1388. doi: 10.1177/1933719118765983. Epub 2018 Apr 16.

DOI:10.1177/1933719118765983
PMID:29656698
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 ( < .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 ( < .05). The expression level of MTNR1B in placenta was significantly higher in the GDM group than in the control group ( < .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], < .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.

摘要

目的

本研究旨在探讨汉族妊娠期糖尿病(GDM)妇女胎盘褪黑素受体 1B(MTNR1B)基因多态性与表达的关系。

方法

本研究采用直接测序法对 215 例 GDM 患者和 243 例健康对照者的 MTNR1B 单核苷酸多态性 rs10830963 进行基因分型。采用免疫组织化学和 Western blot 法检测 MTNR1B 在胎盘组织中的表达。探讨 rs10830963 与 MTNR1B 表达、血浆葡萄糖、胰岛素水平以及血脂水平的关系。

结果

rs10830963 的基因型和等位基因频率在 GDM 患者和对照组之间差异有统计学意义( <.05)。GDM 患者中 GG 和 GC 基因型的空腹血糖、空腹胰岛素和胰岛素抵抗评估模型(HOMA-IR)均显著高于 CC 基因型( <.05)。GDM 组胎盘 MTNR1B 的表达水平明显高于对照组( <.05)。所有 GG 和 GC 基因型的 MTNR1B 表达水平(1.31[0.74])均显著高于 CC 基因型的孕妇(0.92[0.52], <.05)。

结论

MTNR1B 基因多态性 rs10830963 及其蛋白表达水平与汉族 GDM 妇女发生 GDM 的风险增加有关。此外,rs10830963 可能标记了导致汉族 GDM 妇女胰岛素抵抗的分子机制。

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