Association of ulcerative colitis with transcobalamin II gene polymorphisms and serum homocysteine, vitamin B12, and folate levels in Chinese patients

Abstract

It has been reported that abnormal elevation of homocysteine is quite prevalent in ulcerative colitis (UC) patients. We attempted to explore the relationship of UC with transcobalamin II (TCN2) gene polymorphisms and serum homocysteine, vitamin B, and folate levels in Chinese patients. TCN2 (rs1801198, rs9606756) genotypes were detected by the improved multiple ligase detection reaction (iMLDR) technique in 527 UC patients and 574 controls. Moreover, 128 UC patients and 138 controls were randomly selected for the measurement of homocysteine, vitamin B, and folate levels by enzymatic cycling assay or chemiluminescence immunoassay. For TCN2 (rs1801198), the frequency of allele G and combined frequencies of CG and GG genotypes were increased in patients with mild, moderate, and severe UC compared with those with remission UC (all P < 0.001). The average homocysteine level was elevated (10.78 ± 3.33 vs 9.91 ± 2.88 μmol/L, P = 0.024), whereas the average vitamin B and folate levels were reduced (408.66 ± 185.00 vs 457.42 ± 206.47 pg/mL, P = 0.044; 6.81 ± 3.06 vs 8.17 ± 2.58 ng/mL, P < 0.001, respectively) in UC patients than in controls. Compared with controls, the prevalence of hyperhomocysteinemia (HHcy >15.0 μmol/L), vitamin B deficiency (<203.0 pg/mL), and folate deficiency (<4.0 ng/mL) was higher in UC patients (all P < 0.05). Both HHcy and folate deficiency were shown to be independent risk factors for UC (95% CI = 1.206-12.293, P = 0.023; 95% CI = 1.910-11.129, P = 0.001, respectively). TCN2 (rs1801198, rs9606756) mutations might aggravate the severity of UC. HHcy and folate deficiency are independent risk factors for UC.

Association Between MTHFR 677C>T Polymorphism and Vitamin B12 Deficiency: A Case-Control Study

“…Consequently, low levels of vitamin B12 are associated with neurological and hematological disorders such as neural tube defects, cardiovascular diseases, dementia, as well as some types of cancer (8, 16, 28, 34). However, genetic predisposition to vitamin B12 deficiency has been demonstrated in various studies (14, 15, 16, 17, 18, 19, 20, 21, 22). For in stance, vitamin B12 deficiency has been demonstrated by ABCD4 mutations and LMBRD1 mutations (35, 36).…”

“…For instance, mutations and polymorphisms in transport proteins such as transcobalamin TCN, gastric intrinsic factor GIF and metabolic enzymes such as methylenetetrahydrofolate reductase MTHFR have been associated with vitamin B12 deficiency. Other vitamin-B12 related abnormalities like homocysteinemia and neural tube defect (NTD) have also been associated with genetic variants in these genes (13, 14, 15, 16, 17, 18, 19, 20, 21, 22).…”

Efficacy of Novel Aminooxyacetic Acid Prodrugs in Colon Cancer Models: Towards Clinical Translation of the Cystathionine β-Synthase Inhibition Concept

“…Given its importance in normal physiology, it is not surprising that dysregulation of H 2 S homeostasis is implicated in the pathophysiology of many diseases, with some illnesses including atherosclerosis, colitis, type 2 diabetes, psoriasis, and hepatocellular carcinoma exhibiting local and/or systemic suppression of physiological levels of H 2 S, while other maladies (e.g., various forms of shock and inflammation, and Down syndrome) are associated with an aberrant upregulation of H 2 S production [8][9][10][11][12][13][14][15].…”

Effect of imbalance in folate and vitamin B12 in maternal/parental diet on global methylation and regulatory miRNAs

“…LMBRD1 also known as ‘probable lysosomal cobalamin transporter’ is involved in the conversion of B12 into one of two molecules, methyl cobalamin (MeCbl) or adenosyl cobalamin (AdoCbl) which serve as cofactors for methionine synthase 7 . TC-II encodes for proteins known as R binders and is involved in the transport of cobalamin in the cells 8 .…”