Are Genes Connected with Homocysteine Metabolism Associated with Bipolar Disorder?

Abstract

Background: Increased levels of homocysteine have been observed in various psychiatric disorders, among them in schizophrenia, depression and bipolar mood disorder. Of the genes connected with homocysteine metabolism, some studies have found an association between polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and bipolar disorder. The aim of this study was to investigate a possible association between 5 polymorphisms of 4 genes coding enzymes of homocysteine metabolism and bipolar disorder. Method: A total of 120 patients with bipolar disorder (24 male, 96 female) and 167 subjects from the general population (81 male, 86 female) were included in the study. Genotyping was performed for the C677T (rs1801133) and A1298C (rs1801131) polymorphisms of the MTHFR gene, for the T833C polymorphism (rs5742905) of the cystathionine-β-synthase (CBS) gene, for the A2756G polymorphism (rs1805087) of the homocysteine methyltransferase gene, and for the A66G polymorphism (rs1801394) of the methionine synthase reductase (MTRR) gene. Results: An association with bipolar disorder was found for the T833C polymorphism (rs5742905) of the CBS gene. However, in the patient sample, the genotypes of this polymorphism were not in Hardy-Weinberg equilibrium. No relationship to bipolar disorder was obtained for the remaining polymorphisms studied. Conclusions: These results are the first suggesting a possible association between T833C polymorphism (rs5742905) of the CBS gene and bipolar disorder. We were unable to confirm an association between bipolar disorder and C677T polymorphism (rs1801133) of the MTHFR gene, as suggested in some previous studies.

In silico characterization of functional single nucleotide polymorphisms of folate pathway genes

“…Although many other mutations and polymorphisms that disrupt or alter folate metabolism have been reported in the past (Rai et al., ), the present analysis identifies CBS rs5742905, ABCC1 rs45511401, and MTHFR rs1801133 variants as potential candidates for studying disease which is influenced by folate and its metabolism or its downstream processes. These results are in concordance with some of the earlier investigations (Table ) where CBS rs5742905 has been shown to increase the risk of bipolar disorder by 1.89‐fold (Permoda‐Osip et al., ) and also affects hyperactivity in attention‐deficit hyperactivity disorder (ADHD) (Saha et al., ). Interestingly, ABCC1 rs45511401 has been shown to increase the risk of febrile neutropenia in breast cancer patients undergoing 5‐fluorouracil, epirubicin, and cyclophosphamide chemotherapy (Vulsteke et al., ) and doxorubicin‐induced toxicity (Jungsuwadee et al., ).…”

“…The role of MTHFR and CBS gene variations has been evaluated in different human conditions, namely occlusive vascular disease, neural tube defects, colon cancer, adult acute leukemia, spina bifida, bipolar disorders, coronary artery disease, breast cancer, sepsis, preeclampsia, and so on. (Martinez et al., ; Beard & Bearden, ; Masud & Qureshi, ; Permoda‐Osipet al., ; Wu et al., ; Sponholz et al., ; Holwerda et al., ). Although many other mutations and polymorphisms that disrupt or alter folate metabolism have been reported in the past (Rai et al., ), the present analysis identifies CBS rs5742905, ABCC1 rs45511401, and MTHFR rs1801133 variants as potential candidates for studying disease which is influenced by folate and its metabolism or its downstream processes.…”

Homocysteine levels in schizophrenia and affective disorders—focus on cognition

“…As similar to schizophrenia, two common polymorphisms in the MTHFR gene (C677T and A1298C) might increase the risk of bipolar disorder and predict the development of comorbid metabolic syndrome suggesting the existence of common genetic underpinnings (Peerbooms et al, 2011 ; Ellingrod et al, 2012 ). There is also one study showing an association between the T833C polymorphism in the CBS gene and bipolar disorder risk (Permoda-Osip et al, 2014a ).…”

When should a psychiatrist remember to test homocysteine levels? - a literature review

“…The causes of hyperhomocysteinemia are still under investigation. So far, the relationship between genetic changes (resulting in hyperhomocysteinemia) and bipolar disorder, schizophrenia, Alzheimer's disease or depression has been revealed [37,38]. Homocysteine is an underestimated marker that is rarely marked, and in excess it leads to the development of dangerous somatic and mental disorders and diseases.…”

“…The second analyzed mutation is a single nucleotide polymorphism of the CBS gene resulting from the substitution of thymine nucleotide with cytosine in codon 833. Permoda-Osip et al noticed a possible relationship between this genetic change and bipolar disorder [38]. Some data from the literature mention the possible potential of homocysteine as a biomarker of the risk of developing bipolar disorder [39].…”