Investigation of miRNA-binding site variants and risk of gestational diabetes mellitus in Chinese pregnant women
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Abstract
Aims
Emerging evidence suggested genetic factor attributed as a major determinant for the complex pathogenic mechanism of gestational diabetes mellitus (GDM), but the related genetic study was limited. We aimed to investigate the impact of polymorphisms in miRNA-binding sites (miR-binding SNPs) on the risk of GDM in Chinese Han pregnant women.
Methods
We screened GDM susceptibility genes extensively and selected miR-binding SNPs using four bioinformatics software. TaqMan allelic discrimination assays were applied to miR-binding SNPs genotyping in 839 GDM patients and 900 controls.
Results
In total five potential miR-binding SNPs (SLC30A8 rs2466293, INSR rs1366600, INSR rs3745550, KCNJ11 rs5210 and KCNQ1 rs8234) were selected. Our results showed that SLC30A8 rs2466293 [OR 95% CI = 1.455 (1.077, 1.966); P = 0.014] and INSR rs1366600 [OR 95% CI = 2.191 (1.077, 4.455); P = 0.029] increased the risk of GDM after adjusting age in additive model. Furthermore, rs2466293 was found to significantly associate with higher levels of fasting plasma glucose (b dom = 0.054, P dom = 0.032), 2-h OGTT plasma glucose (b dom = 0.069, P dom = 0.007), lower fasting insulin concentrations (b rec = −0.082, P rec = 0.003) and decreased HOMA-B (b rec = −0.067, P rec = 0.015). Additionally, the correlation between rs1366600 and 2-h OGTT plasma glucose (b dom = 0.078, P dom = 0.001) was observed.
Conclusions
Two miR-binding SNPs SLC30A8 rs2466293 and INSR rs1366600 increased GDM susceptibility. Functional studies were required to confirm the underlying mechanism. Our study provided additional insights into the genetic pathogenesis of GDM.
Keywords
Gestational diabetes mellitus Variants miRNA Glucose metabolismNotes
Acknowledgements
We thank for all the participants in this study. The study was funded by research grants from the National Natural Science Foundation of China (Grant No. 81270879) and National Key Program of Clinical Science (WBYZ2011873).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical standard
All procedures performed in this study involving human participants were in accordance with the ethical standards of the Peking Union Medical College Hospital Ethics Committee.
Human and animal rights
The study was conducted in accordance with the principles of the Declaration of Helsinki of 1975, as revised in 2008.
Informed consent
Informed consent was obtained from all patients for being included in the study.
Supplementary material
References
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