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The Association Of Interleukin-6 Gene-572C/G Polymorphism With Coronary Heart Disease

Posted on:2005-09-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:H X FuFull Text:PDF
GTID:1104360125955729Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The causes of coronary heart disease (CHD) have been intensely scrutinized for the last few decades. Since the classic risk factors only explain half of the causes of the patients with CHD, additional risk factors based on molecular genetics are now being sought. It is now clear that inflammation plays an important role in the pathogenesis of CHD. Gene polymorphisms that influence the capacity for producing inflammatory mediators or the capacity of monocytes and lymphocytes to respond to inflammatory stimuli may increase the risk of atherosclerosis and CHD. It is important to research the relationship between gene variants of inflammatory molecules and CHD.Interleukin-6 (IL-6) is a central mediator of the acute-phase response and a primary determinant of hepatic production of C-reactive protein and fibrinogen. It is involved in atherosclerosis and plays a central role in the initiation of CHD. Elevated IL-6 levels are associated with the development and poor outcome of CHD, even with restenosis after percutaneous coronary intervention (PCI). IL-6 gene is a candidate gene for predisposition to risk of CHD. The IL-6 gene, located on chromosome 7p21, spans about 5kb and consists of five exons and four introns. A polymorphism has been discovered, IL-6 gene -572 C/G polymorphism. The present study was conducted to examine whether IL-6 gene -572 C/G polymorphism is functional and involved in the susceptibility to CHD and affects the serum IL-6 levels after PCI. This study included four parts.The first part was designed to study the distribution of IL-6 gene -572 C/G polymorphism in Hubei Hans population. A total of 252 healthy adults were enrolled. Genotypes of the -572 C/G polymorphism were determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method. There was IL-6 gene -572 C/G polymorphism in the test population. -572 CC, CG and GGgenotype frequencies were 67.06%, 31.75% and 1.19%, respectively. -572 C and G allele frequencies were 82.94% and 17.06%, respectively. Polymorphic analyses indicated ethnic differences in the distribution of IL-6 gene - 572 C/G polymorphism. The distribution of IL-6 gene -572 C/G polymorphism in Hubei Hans population was similar to that in Japanese (P>0.05), but significantly different from that in English, French and American population (P<0.001). There were no differences in age, gender, body mass index and levels of blood pressure, blood sugar and serum lipids between subjects with two different genotypes (.P>0.05). In-conclusion, there is IL-6 gene -572 C/G polymorphism in Hubei Hans population. The frequencies of -572 CC genotype and -572 C allele are common, while -572 GG genotype and - 572 G allele frequencies are rare. There are differences in the distribution of IL-6 gene -572 C/G polymorphism among Chinese Hans, Japanese, English, French and American. IL-6 gene -572 C/G polymorphism does not affect body mass index and the levels of blood pressure, blood sugar and serum lipids in Hubei Hans population.The purpose of the second part was to investigate the function of IL-6 gene -572 C/G polymorphism. IL-6 production by peripheral blood mononuclear cells (PBMC) was determined in the healthy subjects with CC genotype (n=\9) and CG genotype (n=11). PBMC were separated by density gradient centrifugation of heparinized venous blood, cultured without oxidized low-density lipoprotein (Ox-LDL) or with 5ug/ml Ox-LDL. The IL-6 concentrations in the culture supernatants after incubation for 3h, 6h, 12h and 24h were measured using an enzyme linked immunosorbent assay (ELISA) kit. In the condition without Ox-LDL, IL-6 production in subjects with two different genotypes increased in a time-dependent manner, achieved peak at 24h. At this time, IL-6 concentrations in the supernatants were significantly higher in subjects with CG genotype than that in subjects with CC genotype (30.36+13.87 Vs 15.78+4.56, P<0.05, unit: pg/ml). Ox-LDL stimulated IL-6 secretion by PBMC in subjects with two different genotypes...
Keywords/Search Tags:Interleukin-6, Coronary heart disease, Gene Polymorphism (Genetics), inflammation, restenosis
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