The current researches on candidate genes for MS are mainly focused on
genes related to lipid metabolism disorders, hypertension and so on,
when these genes related to different components of MS have
polymorphisms or mutations, it may touch some risk factors or protective
factors of MS, thereby affecting the development of MS. In the early
years, researches on TBXAS1 gene mainly focused on inflammation,
breast cancer and other diseases. In recent years, researches on this
gene and diseases such as myocardial infarction, stroke, preeclampsia,
has become a hot spot. Ulrich et al. 27 found that
mutations in the TBXAS1 gene could alter protein function, which
were related to inflammation and angiogenesis. Abraham et al.28 found that the
NC_000007.14:g.139959792T>A mutation of the TBXAS1gene could moderately increase the risk of breast cancer. Lemaitre et
al. 24 found NC_000007.14:g.139959792T>A
was also related to ischemic stroke. Park et al. 29found that the
+16184G> T
polymorphism of TBXAS1 gene and TBXAS1-ht3 polymorphism frequency in
cerebral infarction, especially in patients with small arterial
occlusive cerebral infarction, increased significantly.
In our study, there was polymorphism in the
NC_000007.14:g.139985896C>T in the Han population in
Shandong province of China. Comparison of the genotype and allele
frequency distribution of the population suggested that there was no
association between MS and the different genotypes of
NC_000007.14:g.139985896C>T. However, MS is a syndrome of
abdominal obesity, hyperglycemia, dyslipidemia and hypertension. This
study observed and recorded the main clinical indicators related to the
components of the MS. The results showed that in the MS population,
there was no correlation between
NC_000007.14:g.139985896C>T polymorphism and clinical
indicators. This study further studied the genotype and allele
frequencies and the different components of MS. The results showed that
this gene polymorphism had no relationship with TG, blood pressure, FPG,
abdominal obesity, and HDL-C, suggesting that
NC_000007.14:g.139985896C>T polymorphism has no
correlation with the incidence of MS. But although there was no
difference in HDL-C levels among different genotype carriers, there were
differences in HDL-C levels between the C and T alleles, suggesting that
the C allele may have a regulatory effect on HDL-C. Therefore, is
NC_000007.14:g.139985896C>T related to the prognosis of
MS? To this end, we followed the population for 5 years to observe the
relationship between the gene polymorphism and the prognosis of MS. This
study found that NC_000007.14:g.139985896C>T polymorphism
in the general population and MS population is associated with the
incidence of ischemic stroke, which was similar to Lemaitre’s results
that NC_000007.14:g.139985896C>T polymorphism is
associated with ischemic stroke 24.
Recent studies also found that,TBXAS1 gene polymorphisms had significant association with
large-artery atherosclerosis stroke susceptibility and the level ofTBXAS1 expression 30. A study of Chinese people
found that the TT genotype of TBXAS1 and T allele of
NC_000007.14:g.139845571T>G increase susceptibility to
ischemic stroke 31. However, the population of our
study was more special, which were MS patients. At the same time,
through screening of NC_000007.14:g.139985896C>T
polymorphism and risk factors for ischemic stroke, it was found that the
C allele was an independent protective factor for the incidence of
ischemic stroke in the whole and MS population, individuals who carry
the C allele have a reduced risk of stroke. Carriers of T allele are
more likely to have ischemic stroke, but that was not an independent
risk factor for ischemic stroke in this study, which may be influenced
by other factors and need further study. Therefore, people carrying the
C allele are less likely to suffer from ischemic stroke, which is more
obvious when combined with MS. Patients with T allele should be better
treated for MS to prevent the occurrence and development of ischemic
stroke.
The components of MS, such as hypertension, glucose and lipid
metabolism, are genetically predisposed 10, 11. The
heterogeneity of clinical phenotypes suggests that there may be genetic
heterogeneity in MS, but no candidate genes have been reported could
directly explain the onset and prognosis of MS. These genes mainly
affect the occurrence and development of MS through the intermediate
phenotype of MS development. Therefore, in this study, interaction
analysis was performed of the NC_000007.14:g.139985896C>T
polymorphism and the clinical characteristics of the subjects. Obesity
is a risk factor of stroke 32, the results of this
study showed that there were negative interactions between C allele and
WC in the whole and MS population, suggesting that the C allele is a
protective factor of ischemic stroke. With constant WC, the risk of
ischemic stroke was reduced in carriers of the C allele. Hypertension is
also a risk factor for stroke 32. In the present
study, with the genotype of the whole and MS population unchanged, those
with high SBP or DBP have a high risk of stroke, which is consistent
with previous researches. Abnormal glucose and lipid metabolism are the
main clinical feature of MS. In this study, the C allele had negative
interactions with TG, HDL-C, and FPG. With the same TG, HDL-C, and FPG,
the C allele carriers had a reduced risk of ischemic stroke. It is worth
noting that the interaction of genes and clinical characteristics refers
to combined effect, and cannot simply add the effects of various factors
together. At the same time, a distinction should be made between
biologically relevant and statistically relevant differences. Therefore,
the statistical interactions found by association analysis need further
study of its molecular mechanism to clarify its biological significance.
Some limitations in this study need to be considered. First, the
hypothetical molecular mechanism how
NC_000007.14:g.139985896C>T polymorphism affected the
onset of ischemic stroke was not addressed in the present study. Second,
further validation for the predictive value of this SNP as risk factor
of MS components and pharmacogenetic indicator in independent cohorts.
This study has indicated that NC_000007.14:g.139985896C>T
polymorphism was not associated with the pathogenesis or components of
MS. However, it was related to the incidence of ischemic stroke in the
whole and MS population, individuals who carry the C allele of
NC_000007.14:g.139985896C>T have a reduced risk of stroke.
These results suggest that this locus could be used as a therapeutic
target for MS and providing a basis for genotype-guided individualized
medication.
The authors have no conflicts of interest.