Introduction
Metabolic
syndrome (MS) is a clustering of some cardiovascular risk factors,
including obesity, hypertension, hyperglycemia and dyslipidemia. In
recent years, with the effects of an aging population, overeating, lack
of exercise and other adverse lifestyles, the prevalence of MS has
continued to increase globally. Epidemiological studies in western
countries showed that, the prevalence of MS in adults is about 20-30%1. In China, a survey showed that the prevalence of MS
was approximately 18% -22% 2. As a chronic lifelong
disease, MS is closely related to diabetes and cardiovascular disease.
Previous studies have confirmed that MS can increase the risk of
diabetes by 5 times 3, increased the risk of
cardiovascular events by 2 times 4, and increased
all-cause mortality by 1.5 times 5. In addition, MS is
an important risk factor for stroke, which could increase the risk of
ischemic stroke by a factor of 2 6. Therefore, it is
necessary to study the MS and related diseases.
Studies have shown that 7, multiple risk factors are
related to the onset and prognosis of MS, but even when exposed to the
same environment, some populations are still more prone to MS or target
organ damage than others. Recent studies have found MS has family
aggregation, as well as racial and regional differences8, 9. At the same time, the components of MS, such as
hypertension, abnormal glucose and lipid metabolism, also have a genetic
predisposition 10, 11, which indicate that MS has a
significant genetic susceptibility. Therefore, it is currently believed
that MS is a complex disease with the combined action of genetic factor
and environmental factor, in which genetic factor is internal factor
that play an important role in the development of MS. In recent years,
several susceptibility genes related to MS and its components have been
identified, such as the retinol-binding protein 4 gene12, 13, angiopoietin-like protein gene14, and glucokinase regulatory protein gene15. These genes mainly affect the onset and prognosis
of MS by affecting the intermediate phenotypes of MS, therefore, by
studying the susceptibility genes related to MS, we can not only
elucidate the pathogenesis of the disease from the genetic perspective,
but also screen the susceptible population at an early stage, providing
new ideas and prospects for the comprehensive treatment of MS.
Thromboxane synthase (TS) is a microsomal enzyme that belongs to the
cytochrome P450 (CYP450) family. TS is listed as CYP5 according to the
nomenclature of P450 16, 17. The function of TS is to
catalyze the isomerization of prostaglandin H2 (PGH2) to thromboxane A2
(TXA2). TXA2 is an effective inducer of platelet aggregation, release
and smooth muscle contraction, playing an important role in regulating
vascular tension, maintaining blood fluidity and hemostatic mechanism18. Lack of platelet TS activity can lead to bleeding,
while excess of TXA2 is associated with the pathological process of many
diseases, such as cardiovascular diseases 19. The
human thromboxane A synthase 1 (TBXAS1) gene is located on chromosome
7q3420, 21, including 13 exons and 12
introns21, 22. As its important role in thrombotic
diseases, it has become a research focus in recent years. Oh et al.
reported that the rare allele of
NC_000007.14:g.139971318T>A may play a protective role
against aspirin hypersensitivity via a lower catalytic activity of theTBXAS1 gene 23. Lemaitre et al. studied more
than 30 single nucleotide polymorphisms (SNPs) in the TBXAS1 gene
and found that NC_000007.14:g.139954457C>T,
NC_000007.14:g.139985896C>T,
and NC_000007.14:g.139964799A>C are all related to the
onset of myocardial infarction, and
NC_000007.14:g.139985896C>T is also associated with
ischemic stroke 24. As the risks of cardiovascular and
cerebrovascular disease in MS patients are significantly higher than
that in normal people, and the relationship between this gene and MS has
not been reported, Whether TBXAS1 gene is a susceptible gene for
MS and its components, or plays a role in MS-related damage needs
further exploration and verification. Therefore, we will
study the distribution ofTBXAS1 gene SNPs in the Han population in Shandong, China,
explore the relationship between TBXAS1 gene polymorphisms and
MS, and provide new ideas for the prevention and treatment of MS.
Materials and Methods
Study population
An epidemiological survey about MS was conducted of 21,700 subjects from
January 2007 to December 2007. All participants were from the Han
population in China. According to random sampling, a total of 3072
eligible subjects were obtained, of which 1079 cases were normal
controls, 1993 cases were patients with MS. From January to December
2012, the study subjects were followed up and the endpoint events were
recorded. This study was approved by the ethics committee of Qilu
Hospital of Shandong University. Written informed consent was obtained
from all subjects.
MS was defined according to the joint recommendations of the
International Diabetes Federation, American Heart Association, and
National Heart, Lung, and Blood Institute 25. The
exclusive criteria were: secondary hypertension, severe heart failure,
renal failure or valvular heart disease. Individuals with missing
covariates, missing biochemical data, undetected or discordant genotype
were also excluded. Endpoints: all-cause death, ischemic stroke,
coronary heart disease, myocardial infarction, new-onset diabetes,
new-onset hypertension and new-onset MS.
Demographic data collection, clinical and biological assessment
The clinical data were assessed by questionnaire. Height, weight and
waist circumference were measured and body mass index (BMI) was
calculated. Blood pressure was measured with the use of OMRON HEM-7011
electronic sphygmomanometer (Omron, Japan), SBP and DBP were defined as
the average of three readings. Venous blood samples were obtained from
all subjects after fasting for at least 12 hours for biochemical
determination and DNA extraction.