title: Platelet-specific collagen receptor glycoprotein VI gene variants affect recurrent pregnancy loss.
abstract: OBJECTIVE
  To determine whether platelet-specific collagen receptor glycoprotein VI (GP6) gene variants are associated with recurrent miscarriages (RM).
  
  
  METHODS
  Genetic association study.
  
  
  METHODS
  Tertiary care referral hospital.
  
  
  METHODS
  A total of 200 women with at least three unexplained spontaneous abortions before 20 weeks of gestation and 300 healthy parous women.
  
  
  METHODS
  Determination of variants of GP6 single-nucleotide polymorphisms (SNPs) namely; rs1671153, rs1654410, rs1654419, and rs1613662 was based on polymerase chain reaction-restriction fragment-length polymorphism.
  
  
  METHODS
  Genotypes and haplotypes frequencies were compared in RM case subjects versus control subjects.
  
  
  RESULTS
  We observed significantly higher occurrence of rare alleles of SNPs in GP6, namely, rs1671153, rs1654410, rs1654419, and rs1613662, among RM cases, revealing risk association for fetal losses. The synergistic effects of haplotype combinations were also evaluated and showed that four haplotypes G-T-G-G, T-C-A-A, G-C-G-A, and G-T-A-A were more prevalent among RM cases, revealing increased risk for fetal losses. In silico analysis revealed that GP6 has an impact on biologic pathways and significant influence in collagen binding. Gene-gene interaction network analysis revealed that GP6 consisted of a total of 25 interactions with 13 genes in the human genome.
  
  
  CONCLUSIONS
  These results suggest that variants of GP6 SNPs, namely, rs1671153, rs1654410, rs1654419, and rs1613662, may be associated with risk of recurrent miscarriage. In silico analyses demonstrated the influence of GP6 in biologic pathways, molecular function, including collagen binding, and gene-gene interaction in the human genome.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Anjurani
authors.initials: A
authors.lastname: Siddesh
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Farah
authors.initials: F
authors.lastname: Parveen
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Maneesh Kumar
authors.initials: MK
authors.lastname: Misra
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Shubha R
authors.initials: SR
authors.lastname: Phadke
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Electronic address: suraksha@sgpgi.ac.in.
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D016022:Case-Control Studies; D003198:Computer Simulation; D005260:Female; D005787:Gene Frequency; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors
chemical_list: D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI
keywords: Recurrent miscarriages; fetal losses; glycoprotein VI; platelets; single-nucleotide polymorphism