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.