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Since coronary artery spasm in 1959 for the first time since Prinzmetal and other researchers described in coronary heart disease, especially acute coronary syndrome status to get more and more widely recognized. Coronary artery spasm occurred on the basis of atherosclerosis, but positively correlated with the degree of coronary artery stenosis does not necessarily was, and most occur in mild to moderate stenosis. A coronary spasm population studies have shown that smoking and dyslipidemia is an important risk factor for coronary artery spasm, where smoking is an independent risk factor for coronary artery spasm, and the risk of coronary artery spasm can be increased by 4.2 times, dyslipidemia coronal 2.3 times increased risk of arterial spasm. Gender, age, high blood pressure, electrocardiogram the treadmill test positive with coronary artery spasm was no significant correlation. Atherosclerosis, the other two major risk factors for diabetes and high blood pressure does not seem to significantly increase the risk of coronary artery spasm. Therefore, the positive control smoking and improve dyslipidemia not only effective in the prevention of atherosclerosis, but also conducive to the prevention and treatment of coronary artery spasm. Coronary artery spasm provocation test high-risk groups for coronary artery spasm coronary muscle bridge, narrow the systolic blood vessel such patients due to muscle bridge, and also have the characteristics of typical exertional angina. Diabetes, insulin resistance, hypertension, coronary artery spasm relationship between the results of the current study is not exactly the same, pending further clarify the relationship between them. The exact mechanism of coronary artery spasm has not yet clarified, may be associated with the following pathophysiological mechanisms. Vascular endothelial cell structure and function disorders, mainly to reduce nitric oxide synthesis and secretion of endothelin secretion, leading to vasomotor regulation dysfunction. Molecular biological mechanisms involved in oxidative stress, endothelin-1 and nitric oxide synthase gene polymorphism may include oxidative stress, dyslipidemia, smoking, and other risk factors, often start in vascular endothelial cells The damage process. 2. Increased contractile response of vascular smooth muscle cells, vascular smooth muscle cells of the contractile response to agonists was excessive, may be associated with myosin light chain phosphorylation regulation of enzymes gene mutations also may be associated with inflammatory cytokines such as interleukin-6 stimulus. 3. Imbalance in the autonomic nervous system function, mainly to reduce vagal tone increased sympathetic activity. In the case of non-the corresponding sympathetic activity contend, the vagus nerve tension is too high lead to coronary artery at different levels of spasticity, severe cases can present a typical coronary spastic angina. Wherein the disorder of the structure and function of vascular endothelial cells, mainly into vascular contraction between the factor and vascular relaxing factor imbalance is considered to be an important factor to cause coronary spasm. Mainly for the reduction of elevated levels of endothelin-1 and NO levels. Increased levels of endothelin-1 has been widespread concern, preliminary studies show that in our group, coronary spasm group of endothelin-1 level higher than the healthy control group (108.71 ± 8.26,93.02 ± 8.13, t = 2.219, P lt; 0.05). Encoding endothelin-1 gene EDN1, human EDN1 gene is located on chromosome 6p23 a p24 chromosome ends, close to the HLA-A, B, and the DRB closely with D6S89 chain length of 5.5 kb of exon 5 outside and four introns, encoding mature ET-1 peptide sequence is in exon 2. Endothelin-1 gene has been found to exist six polymorphisms, T / G transversion in the transcription initiation site 1370 points; exon insertion or deletion of a 138 point A; intron 1, 1932 point of G / A conversion; intron 2 of the 3539 T / C point conversion: exon 5 of the 5665 point G / T transversion, affecting 61 nucleotides, resulting in 198 password sub-lysine / aspartic acid shift (Lysl98Asn); intron 4 of the 8000 point T / C conversion. Endothelin-1 is mainly in the gene expression level can be adjusted. The number of single nucleotide polymorphisms (SNPs) have been identified, introns and exons related sites in the promoter gene polymorphism was found to increase with chronic heart failure, high blood pressure, ventricular arrhythmia, and out-of-school and other cardiovascular disease risk. Lee et al reported that Korea coronary spasm crowd of endothelin-1 gene polymorphism, suggesting that the changes of endothelin-1 may be associated with genetic polymorphisms. Foreign studies have shown that the plasma level of endothelin-1 exon -1 138delA (rs10478694), the intron-4G8002A (rs2071942) and outside the exon-5G5665T (rs5370) three loci gene polymorphism is closely related to the selected the three points are used to assess the endothelin-1 gene polymorphism change. Based on above understanding, the the wooden study of 100 patients with coronary artery spasm patients and 120 healthy control subjects were the three loci endothelin-1 genotype and allele parting research, in order to find the endothelin-1 gene genetic correlation may exist between the polymorphism and coronary artery spasm. Objective 1. Explore the frequency distribution of the endothelin-1 gene polymorphism 2. Explore the relationship between the object and method objects in the endothelin-1 gene polymorphism and coronary spasm study from December 2008 to 2010 months of Guangzhou Military Command General Hospital Cardiology inpatient or outpatient and healthy population selected. Coronary artery spasm group inclusion criteria: December 2008 to March 2010 in our hospital after acetylcholine challenge test and / or non-invasive diagnostic methods clear diagnosis for patients with coronary artery spasm, a total of 100 cases. Acetylcholine provocation test positive diagnostic criteria for clinical manifestations: ① resting chest tightness or chest pain; ② coronary angiography showed no stenosis; ③ intracoronary injection of acetylcholine-induced coronary artery spasm caused by stenosis of more than 90%, with similar the onset of the usual symptoms of chest pain or chest tightness, spasm relieve the symptoms disappear. The non-invasive diagnostic standard: meet the following three conditions were diagnosed at the same time as coronary artery spasm: clinical clinical manifestations of chest tightness or chest pain at rest, positive ECG exercise test was negative or after exercise radionuclide perfusion myocardial scintigraphy presents anti to re-distribution. Health Groups: screening healthy people in our hospital, a total of 120 cases. Requirements of the examination object no chest pain, chest tightness, clinical manifestations, after a routine examination and ECG exercise test, radionuclide perfusion myocardial perfusion imaging and special examination to rule out coronary heart disease, and the age and gender distribution of coronary artery spasm crowd Basic match. Coronary artery spasm group and the healthy control subjects are unrelated Han Chinese people. Exclusion criteria were: associated with bronchial asthma, systemic infection, clearly diagnosed or confirm the diagnosis, but patients with symptoms of gastrointestinal diseases. Method any time to take subjects cubital vein 1m1, placed in EDTA-Na2 anticoagulant tube human blood DNA extraction kit steps extracted from white blood genomic DNA polymerase chain reaction (PCR), commissioned by Shanghai Invitrogen Biotechnology Co., Ltd. direct sequencing of the corresponding sites of the sequencing and SNP locus genotyping, PCR instrument ABi9700, sequencing the 3730XL-type DNA sequencing instrument. Difference between the two-sample t-test was used to compare the coronary spasm group and control subjects age and clinical characteristics of indicators, heterogeneity of variance using Satterthwaite approximate t test; χ2 test was used to compare the two independent sample rates of coronary spasm group and than the gender composition of the control group subjects, hypertension, diabetes, smoking, alcohol consumption differences in incidence; genotype and allele frequencies used to compare two independent sample rate compared χ2 test. P lt; 0.05 indicates that the difference was statistically significant. Results 1. Coronary spasm group and healthy people group were detected in exon -1 138delA, the 4A/4A wild-type, 4A/3A heterozygous, 3A/3A three mutant genotype, intron - 4G8002A G / G wild type G / A heterozygous genotype A / A mutant three genotypes, the The exon-5G5665T G / G wild-type, G / T heterozygous type, T / T mutant genotypes. Coronary artery spasm group 4A/4A, 4A/3A, 3A/3A genotype frequencies were 2.5%, 20.8%, 76.7%; healthy people group compared to 8%, 30%, 62%. Coronary artery spasm group 4A and 3A allele frequencies were 12.9%, 87.1%; healthy people group compared with 23% and 77%. The distribution of genotypes and allele frequencies in the two groups there are significant differences (Wald = 9.133, P = 0.003; x2 = 7.683, P = 0.006). Coronary spasm group GG, GA, AA genotype frequency were 63.3%, 33.4%, 3.3%; healthy people group compared with 47%, 41%, 12%. Coronary artery spasm group G and A allele frequencies were 80%, 20%; healthy people group compared to 67.5% and 32.5%. Genotype frequency distribution in the two groups showed no significant difference (Wald = 0.333, P = 0.564), allele frequencies in the two groups there is a significant difference (χ 2 = 8.931, P = 0.003). Coronary spasm group GG, GT, TT genotype frequency were 65%, 29.2%, 5.8%; healthy people group compared with 43%, 46%, 11%. Coronary spasm group G and T allele frequencies were 79.6%, 20.4%; healthy people group compared with 66%, 34%. The genotype and allele frequencies in the two groups, there were significant differences (Wald = 6.916, P = 0.009; x2 = 10.311, P = 0.001). 3.3AGG singlemode samples in the low frequency of coronary spasm group than in healthy people group (0.47 vs 0.65) difference was statistically significant (x2 = 14.406, P (0.001, odds ratio (OR) = 0.475) the conclusion 1.BMI, smoking risk factors for coronary artery spasm (Wald = 24.161, P lt; 0.001,95% CI 2.657-9.751; Wald = 22.998, P lt; 0.001,95% CI 3.427-18.805), age, gender, The proportion of lipid levels, high blood pressure and diabetes, drinking or not the incidence of coronary artery spasm was no significant correlation. Han population endothelin-1 gene polymorphism in exon -1 138delA, 4A/4A wild type, 4A/3A heterozygous, 3A/3A three mutant genotype, intron-4G8002A three mutant genotype G / G wild-type, G / A heterozygous, A / A, exon the sub-5G5665T G / G wild-type, heterozygous G / T, T / T mutant three genotypes. coronary spasm group and the healthy control group, endothelin-1 exon -1 138 the delA (rs10478694), intron-4G8002A (rs2071942) and exon sub-5G5665T (rs5370) allele frequency distribution there are significant differences in endothelin-1 exon -1138 delA (rs10478694) and exon sub-5G5665T (rs5370) genotype frequency distribution, there are significant differences, the intron-4G8002A (rs2071942) genotype frequency distribution was no significant difference, suggesting that coronary artery spasm may occur with more than three loci polymorphism . coronary artery spasm group and the healthy control group, through the analysis of single-mode sample, 3A/G8002/G5665 allele of the incidence of coronary artery spasm protective effect (χ2 = 14.406, P lt; 0.001, OR = 0.475)
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