Homocysteine is a chemical compound with
the formula HSCH2CH2CH(NH2)CO2H and is a
methylation of cells within the process of intermediate
products. The change of plasma Hcy concentration can
directly affect the genomic DNA methylation, which
tends to repress gene expression while demethylation
or hypomethylation activates the gene expression. Research has revealed that hyperhomocycteine
can lead to low genomic DNA methylation, which
can be the source of many tumors and certain
autoimmune diseases.
2,3 Other research revealed
that the plasma Hcy concentration of systemic
lupus erythematosus (SLE), Behçet's disease (BD),
and systemic sclerosis patients increased much
more than normal.
4-6 The relevance of the present
study with regard to plasma Hcy concentration
and AS is still in the start-up phase. Ankylosing
spondylitis patients with hyperhomocysteine have
been reported,
7-9 and recent research has shown
that the plasma Hcy level is not correlated with AS
activation.
10,11 However, the results of our study
also showed that the plasma Hcy concentration in
AS was significantly higher than in the controls.
The exact mechanism of hyperhomocycteine in
AS is currently not very clear, but study results
show that hyperhomocycteine can enhance the
activation of inflammatory cytokines and trigger
the autoimmune mechanism.
1,12 Homocysteine
can also modify HLA antigens in the T cytotoxic
lymphocytes, such as the HLA-B27 molecule and
other surface molecules, resulting in functional
abnormalities of CD4 + T cells that leads to
the occurrence of AS.
12 Homocycteine is the
metabolite of DNA methylation. The excessive
accumulation of metabolic products will inhibit
the DNA methylation process and reduce the level
of DNA methylation, resulting in abnormal gene
expression. Genes expressed differentially may play
an important role in the development and growth
of AS. A lack of vitamins B6, B12, and folic acid
can result in hyperhomocycteine. Therefore, we
speculated that the hyperhomocycteine might also,
in turn, interfere with the level of methylation
in the MTHFR gene promoter region and affect
the expression of mRNA. However, whether the
interference is the cause of DNA hypermethylation
or hypomethylation has not yet to be reported.
The modification of these two different ways also
represents two different pathophysiologies which
must be determined by further study.
The key enzyme in the Hcy metabolism process
is MTHFR, and the MTHFR gene 677 C/T mutation
is common and can produce variations based on
Hinf I restriction enzyme digestion sites. Hence,
the heat sensitivity of MTHFR results in changes
in the activity of decline and improves the level of
plasma Hcy.13 The MTHFR gene polymorphism
and folic acid metabolism can be damaged, leading to increased concentrations of plasma Hcy. Our
study observed that the plasma Hcy level of the T/T
genotype was significantly higher than that of the
C/T or C/C genotype in AS. The results showed
that the T/T genotype is closely related to increased
plasma Hcy concentration. It is worth noting that
the T/T genotype in the AS group was significantly
higher than those in the controls, but it can not be
stated for certain that the MTHFR T/T genotype is
a susceptibile gene to AS. This hypothesis would
need to be studied further.
The relationship between the gene polymorphism
of MTHFR C677T and rheumatic diseases has
recently been researched. Koubaa et al.14 in their
study results showed that the ratio of T/T genotype
in BD patients compared with the control group
was significantly different, and this was related
to higher concentrations of plasma Hcy. Marasini
et al.6 did not support the point that the MTHFR
C677T gene mutation increases the susceptibility
of patients to systemic sclerosis, and at present,
there are very few study reports about the gene
polymorphism of MTHFR C677T with AS. Our
research showed that there was no difference
between the frequency distribution of the MTHFR
genotype C/C and the C/T gene in the AS group
and the control group, but the ratio of the T/T
genotype mutation was different in the AS and the
controls. In the treatment of cancer and rheumatic
diseases, the polymorphism of MTHFR C677T can
increase the incidence of methotrexate toxicity, but
folic acid supplements can reduce the toxicity of
methotrexate and do not affect the treatment.15,16
This prompted us to hypothesize that certain
nutritional factors may be related to the incidence
and treatment of AS. It is likely that a complicated
process related to the control of gene cytokines and
other factors has led to the incidence of AS, but the
specific mechanisms still need further study.
In short, our research showed that plasma Hcy
concentration in AS patients was significantly
higher than normal. The MTHFR gene T/T
mutation is an important mechanism which has an
impact on hyperhomocysteine, and this mutation
may be related to the occurrence of AS.
Acknowledgements
We here by express our thanks to a Major Project Grant
of Frontiers in Sciences, Central South University
(Ministry of Education of China).
Declaration of conflicting interests
The authors declared no conflicts of interest with
respect to the authorship and/or publication of this
article.
Funding
The authors declared that this work was supported by a
major project grant from Frontiers in Sciences, Central
South University (Ministry of Education of China).
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