title: Investigation of miRNA-binding site variants and risk of gestational diabetes mellitus in Chinese pregnant women.
abstract: OBJECTIVE
  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 (bdom= 0.054, Pdom= 0.032), 2-h OGTT plasma glucose (bdom= 0.069, Pdom= 0.007), lower fasting insulin concentrations (brec= -0.082, Prec= 0.003) and decreased HOMA-B (brec= -0.067, Prec= 0.015). Additionally, the correlation between rs1366600 and 2-h OGTT plasma glucose (bdom= 0.078, Pdom= 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.
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu Yuan No. 1, Dongcheng District, Beijing, 100730, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu Yuan No. 1, Dongcheng District, Beijing, 100730, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Liangkun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu Yuan No. 1, Dongcheng District, Beijing, 100730, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Ping
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu Yuan No. 1, Dongcheng District, Beijing, 100730, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu Yuan No. 1, Dongcheng District, Beijing, 100730, China.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Mao
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu Yuan No. 1, Dongcheng District, Beijing, 100730, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu Yuan No. 1, Dongcheng District, Beijing, 100730, China. nm_pumch@aliyun.com.
authors.forename: Min
authors.initials: M
authors.lastname: Nie
mesh_terms: D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002681:China; D016640:Diabetes, Gestational / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D000075703:Zinc Transporter 8
chemical_list: D015703:Antigens, CD; D001786:Blood Glucose; D027682:Cation Transport Proteins; D007328:Insulin; D035683:MicroRNAs; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C435941:INSR protein, human; D011972:Receptor, Insulin
keywords: Gestational diabetes mellitus; Glucose metabolism; Variants; miRNA