title: Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation.
abstract: BACKGROUND
  Glutathione S-transferases (GSTM1, GSTT1, and GSTP1) and methylenetetrahydrofolate reductase (MTHFR) are important enzymes for protection against oxidative stress. In addition, MTHFR has an essential role in DNA synthesis, repair, and methylation. Their polymorphisms have been implicated in the pathogenesis of ulcerative colitis (UC). The aim of the present study was to investigate the role of selected polymorphisms in these genes in the development of UC in the Moldavian population.
  
  
  METHODS
  In a case-control study including 128 UC patients and 136 healthy individuals, GSTM1 and GSTT1 genotypes (polymorphic deletions) were determined using multiplex polymerase chain reaction (PCR). The GSTP1 rs1695 (Ile105Val), MTHFR rs1801133 (C677T), and MTHFR rs1801131 (A1298C) polymorphisms were studied with restriction fragment length polymorphism (RFLP) analysis. Genotype-phenotype correlations were examined using logistic regression analysis.
  
  
  RESULTS
  None of the genotypes, either alone or in combination, showed a strong association with UC. The case-only sub-phenotypic association analysis showed an association of the MTHFR rs1801133 polymorphism with the extent of UC under co-dominant (p corrected = 0.040) and recessive (p corrected = 0.020; OR = 0.15; CI = 0.04-0.63) genetic models. Also, an association between the MTHFR rs1801131 polymorphism and the severity of UC was reported for the over-dominant model (p corrected = 0.023; coefficient = 0.32; 95% CI = 0.10-0.54).
  
  
  CONCLUSIONS
  The GST and MTHFR genotypes do not seem to be a relevant risk factor for UC in our sample. There was, however, evidence that variants in MTHFR may influence the clinical features in UC patients. Additional larger studies investigating the relationship between GST and MTHFR polymorphisms and UC are required.
authors: Laboratory of Human Genetics, Institute of Phthisiopneumology, Kishinev, Republic of Moldova.
authors: Alexander
authors: A
authors: Varzari
authors: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Igor V
authors: IV
authors: Deyneko
authors: Laboratory of Human Genetics, Institute of Phthisiopneumology, Kishinev, Republic of Moldova.
authors: Elena
authors: E
authors: Tudor
authors: Department of Gastroenterology, State University of Medicine and Pharmacy, Kishinev, Republic of Moldova.
authors: Svetlana
authors: S
authors: Turcan
keywords: GST, Glutathione S-transferase; Genetic polymorphism; Glutathione S-transferases; HWE, Hardy–Weinberg equilibrium; IBD, Inflammatory bowel disease; MTHFR, Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate reductase; Moldavian population; PCR, Polymerase chain reaction; RFLP, Restriction fragment length polymorphism; SAM, S-adenosyl methionine; SNP, Single nucleotide polymorphism; Susceptibility; UC, Ulcerative colitis; Ulcerative colitis; n, Total number