title: Polymorphisms in MTHFR, MTHFD, and PAI-1 and recurrent miscarriage among North Indian women.
abstract: OBJECTIVE
  The aim of this study was to investigate the association between MTHFR C677T, A1298C, MTHFD G1958A and plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism among first trimester recurrent miscarriages.
  
  
  METHODS
  DNA was extracted from peripheral blood samples from 200 patients and 300 controls. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and sequencing were used to identify the polymorphisms. We have analyzed the frequencies, odds ratio, Hardy-Weinberg equilibrium.
  
  
  RESULTS
  MTHFR C677T, A1298C, and MTHFD G1958A variant alleles were found to be significantly more prevalent in patients than control. However, variant genotype of MTHFR C677T (OR = 2.54; 95 % CI = 1.23-5.24; p value = 0.014), 1298C (OR = 2.23; 95 % CI = 1.09-4.52; p value = 0.028), and MTHFD-1958 showed significant association with pregnancy loss (OR = 2.36; 95 % CI = 1.39-4.02; p value = 0.002). Both MTHFR 677 and MTHFD 1958 showed susceptible effect under recessive model of inheritance. PAI-1 mutations showed no significance.
  
  
  CONCLUSIONS
  We observed significant susceptible effects of MTHFR C677T, A1298C, and MTHFD G1958A among RM cases. Our data points toward the multifactorial nature of the recurrent miscarriage as relative contribution of variant genotype of MTHFR C677T is only twofold and further decreased to only onefold, and MTHFD-1958 lost its significance upon meta-analysis.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareli Road, Lucknow, UP, 226014, India.
authors.forename: Farah
authors.initials: F
authors.lastname: Parveen
authors.forename: Moni
authors.initials: M
authors.lastname: Tuteja
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006801:Humans; D007194:India; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)