Association of homocysteine with ankylosing spondylitis: a systematic review and meta-analysis

Abstract

Background Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.

Genetic factors involved in the co‑occurrence of endometriosis with ankylosing spondylitis (Review)

“…The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene is located in chromosome 1p36.3, encoding a key rate-limiting, regulatory enzyme in folate and homocysteine metabolism, which catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (131). The MTHFR rs1801133 (ala222Val) SnP, which is located in exon 4, has been found to be significantly associated with both aS and endometriosis (81)(82)(83). it has been previously suggested that polymorphisms in the MTHFR gene may result in alterations in gene expression levels and protein function, thus leading to an abnormal metabolism of 5,10-methylenetetrahydrofolate (82,83).…”

“…The MTHFR rs1801133 (ala222Val) SnP, which is located in exon 4, has been found to be significantly associated with both aS and endometriosis (81)(82)(83). it has been previously suggested that polymorphisms in the MTHFR gene may result in alterations in gene expression levels and protein function, thus leading to an abnormal metabolism of 5,10-methylenetetrahydrofolate (82,83). Thus, the c677T missense mutation, which has been characterized as a thermally unstable one, probably influences the thermostability and activity of MHTFr protein, while it has been also reported that the rs1801133 T allele results in elevated plasma homocysteine levels, which, in combination with endothelial injury and vascular inflammation, may result in the development of cardiovascular disease, a well-known comorbidity of endometriosis (13,132).…”