Genetic polymorphism of methylenetetrahydrofolate reductase G1793A, hyperhomocysteinemia, and folate deficiency correlate with ulcerative colitis in central China

J Gastroenterol Hepatol. 2010 Jun;25(6):1157-61. doi: 10.1111/j.1440-1746.2010.06286.x.

Abstract

Background and aims: Methylenetetrahydrofolate reductase (MTHFR) encoding genes were associated with ulcerative colitis in Chinese in our previous study. We further studied association of a new polymorphism of MTHFR G1793A with ulcerative colitis and assessed relationship of this polymorphism with hyperhomocysteinemia (HHcy, > or = 15 mmol/L) and deficiency of folate (< or = 7 nmol/L) and vitamin B(12) (< or = 150 pmol/L) in a cohort of patients with ulcerative colitis in central China.

Methods: A total of 252 patients and 654 healthy controls were recruited. Polymorphism of MTHFR G1793A was examined using a polymerase chain reaction-restriction fragment length polymorphism method. Plasma levels of homocysteine (Hcy), folate and vitamin B(12) were determined by enzymatic cycling assay and corpuscle immune chemiluminescence assay, respectively.

Results: Frequencies of alleles and genotypes in MTHFR G1793A gene differed significantly between ulcerative colitis patients and the healthy controls (20.83% vs 10.47%, 95% confidence interval [CI]: 1.703-2.972, P = 0.0006; 40.48% vs 19.88%, 95% CI: 1.997-3.761, P = 0.0002, respectively). Plasma Hcy levels were higher and folate and vitamin B(12) concentrations were lower in the patients than in the healthy controls (21.72 +/- 6.59 vs 12.47 +/- 5.02, 95% CI: -10.93--7.58, P < 0.0001; 11.25 +/- 6.19 vs 15.28 +/- 7.72, 95% CI: 2.03-6.04; P < 0.001; 322.81 +/- 128.47 vs 442.59 +/- 129.36, 95% CI: 62.61-136.95, P < 0.0001, respectively). HHcy and folate deficiency were more prevalent in patients with ulcerative colitis (45.32% vs 26.17%, 95% CI: 1.285-4.378, P = 0.005; 30.68% vs 13.0%, 95% CI: 1.416-6.197, P = 0.003, respectively).

Conclusions: MTHFR G1793A gene polymorphism, HHcy, folate deficiency and low vitamin B(12) concentration were associated with ulcerative colitis in central China. Our findings demonstrate that the Hcy-related gene and metabolites are involved in pathogenesis of ulcerative colitis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • China / epidemiology
  • Colitis, Ulcerative / complications
  • Colitis, Ulcerative / enzymology
  • Colitis, Ulcerative / genetics*
  • DNA / genetics*
  • Female
  • Folic Acid / metabolism*
  • Folic Acid Deficiency / enzymology
  • Folic Acid Deficiency / epidemiology
  • Folic Acid Deficiency / etiology*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / enzymology
  • Hyperhomocysteinemia / epidemiology
  • Hyperhomocysteinemia / etiology*
  • Immunoenzyme Techniques
  • Male
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics*
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / metabolism
  • Middle Aged
  • Polymorphism, Genetic*
  • Prevalence
  • Vitamin B 12 / blood

Substances

  • Homocysteine
  • DNA
  • Folic Acid
  • Methylenetetrahydrofolate Dehydrogenase (NADP)
  • Vitamin B 12