| Background:Coronary heart disease (CHD), one of the most common chronic diseases in this world, ranks near the top of the list of the most mortal diseases not only in China but also in other cultures. It is caused by multiple genetic and environmental factors, or interactions among these factors. However, the exact pathogenesis of CHD is unclear. With the completion of the single nucleotide polymorphisms (SNP) map and the size of the human genome sequencing project, the association studies between SNP and diseases, especially the association studies between SNPs and complex diseases become a hot research in the world. Based on the results of GWAS studies, the ABO gene and ADAMTS7 gene are selected in this study, both of which their sites have not yet been confirmed in Chinese Han population. We assessed the association between the SNPs and risk of CHD in case-control studies in Han population, discovery areas which may be related to the pathogenesis of CHD located on the ABO gene and ADAMTS7 genes.Soluble E-selectin (sE-seletcin, CD62) is one of the selectin family members of adhesion molecules. The study reports that adhesion molecules may be involved in inflammatory diseases as inflammatory inlammatroy cytokines. GWAS shows that there is a association between ABO gene and sE-selectin. However, the studies about the association between the molecules and the pathogenesis of CHD, and the molecules and susceptibility such as ABO gene working together to become the marker of CHD are yet to be determined.Methods:10 SNPs are selected as the research subject, which are located on ABO (s8176751, rs630014, rs566183, rs568203, rs651007, rs579459 and rs8176635) and ADAMTS7 (rs3825807, rs922693 and rs 11634042) gene. All the participants provided blood subject and questionnaire information.1. SNP genotypes have been test the Sequenom MassArray t 2. Enzyme linked immunosorbent assay have been test sE-selectin level.Result:(1) rs8176635 is significantly associated with CHD in Chinese Han population (P=0.02), at the same time, TT genotype carriers has a lower risk of CHD, compared with the CC genotype carriers (OR=0.55, 95%CI:0.31-0.96, P=0.04). However, there is no statistical significance between 10 SNP and CHD after adjustment for other risk factors (P>0.05). rs922693 is significantly associated with arrhythmia (x2=10.75, P=0.005). TT genotype carriers have a higher risk of arrhythmia than CT genotype carriers and AA genotype carriers (P=0.00,0.04;OR=0.16,0.04; 95%CI:0.51-0.52,0.01-0.95).The study shows that the ABO gene(rs630014 is related to premature CHD(OR=0.32; 95%CI:0.14-0.74, P<0.05).(2) The haplotype analysis argues only 7 SNPs locate in the ABO gene joint, and there was no significance between haplotypes and the risk of CHD compared with the highest frequency GCGCCAC haplotype (P>0.05). As regard to the only 3 SNPs located in the ADAMTS7 gene joint, TTT haplotype carries enjoys a higher risk of CHD compared to the highest frequency TCC haplotype(OR=8.62,95%CI:4.64-16.01, P=2.95×10-4).(3) The plasma sE-selectin level of myocardial infarction group (94.82±144.40μg/mL) is higher than the angina pectoris group (94.82±144.40μg/mL). A significant difference has been detected in the two groups (P<0.05). (4) With regard to CHD patients with angina pectoris, rs8176751 is significantly associated with sE-selectin (P=0.02). AG carries (71.97±113.95μg/mL) and GG carries (87.52±119.28μg/mL) have lower sE-seletin lever than the highest frequency genotype AA (354.23±450.37μg/mL) (P<0.05).Conclusions:(1) rs8176635 located in ABO gene is related with CHD. (2) Genetic variation loci rs922693 located in ADAMTS7 gene is related to arrhythmia. (3)ABO and ADAMTS7 genes are related to premature CHD. (4) sE-selectin could be an index to measure onset and prognosis of CHD. |
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