Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation

Abstract

BackgroundGlutathione 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.MethodsIn 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.ResultsNone 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).ConclusionThe 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.

RNA-sequencing study of peripheral blood mononuclear cells in sporadic Ménière's disease patients: possible contribution of immunologic dysfunction to the development of this disorder

“…Several studies have suggested that GSTM1 was associated with higher oxidative stress and increased risk for inflammatory diseases, including rheumatoid arthritis [50], systemic lupus erythematosus [51], ulcerative colitis [52], ankylosing spondylitis [5] and inflammatory bowel disease [6]. Several studies have suggested that GSTM1 was associated with higher oxidative stress and increased risk for inflammatory diseases, including rheumatoid arthritis [50], systemic lupus erythematosus [51], ulcerative colitis [52], ankylosing spondylitis [5] and inflammatory bowel disease [6].…”

“…Interestingly, it is noteworthy that MD patients demonstrated higher levels of GSTM1 transcripts relative to controls. Several studies have suggested that GSTM1 was associated with higher oxidative stress and increased risk for inflammatory diseases, including rheumatoid arthritis [50], systemic lupus erythematosus [51], ulcerative colitis [52], ankylosing spondylitis [5] and inflammatory bowel disease [6]. In addition, the increased frequency of HLA and GSTM1 plays an important role in the alloimmune responses of renal transplant recipients [53].…”

Candidate SNP Markers of Atherogenesis Significantly Shifting the Affinity of TATA-Binding Protein for Human Gene Promoters Show Stabilizing Natural Selection as a Sum of Neutral Drift Accelerating Atherogenesis and Directional Natural Selection Slowing It

“…The key concept of 4P medicine [9] is a clinical SNP marker of a given disease; alleles of this SNP allow to statistically significantly distinguish between representative cohorts of patients with this disease and conventionally healthy volunteers as the only acceptable criterion; this is because it quantifies the expected likelihood of a medical error associated with each clinical SNP marker used (see, e.g., in [22]). Nonetheless, it takes too much time, manual labor, and money to test how each of 10 10 human SNPs [14] affects each of 55,000 diseases (see ICD-11 [23]), and why should we if Kimura's theory [24] and Haldane's dilemma [25] predict no phenotypic manifestations for the vast majority of such SNPs.…”

Analysis of genetic polymorphisms of glutathione S‐transferase (GSTP1, GSTM1, and GSTT1) in Polish patients with systemic sclerosis

“…It has been evaluated that the null GSTM1 genotype is present in 40%‐60% of individuals of Caucasian origin, whereas the frequency of the null GSTT1 genotype in the Caucasian population is 10%‐20%. Moreover, carriers of the deletion of both genes ( GSTM1 (‐) and GSTT1 (‐)) account for about 8% …”