| Background and AimCoronary heart disease (CHD) is an complicated disease that can threaten people's health. The pathological hypercholesterolemia is important mechanism of CHD is comp although in approximately 50 percent of patients with cardiovascular disease, However, the underlying pathogenic mechanisms have not been fully understood, although the interactions between environmental, atherosclerosis and multiple genetic components are likely to be involved. Inflammatory is very important in the formation of the lesion, influence the whole process.The main defining pathologic feature of CHD is atherosclerosis. Recently, there is growing evidence for the contribution of genetic polymorphisms to interindividual difference in the regulatory mechanisms of inflammatory cytokine production. Therefore, particular variant cytokine genotypes might contribute to the predisposition to atherosclerosis, exacerbate granuloma formation, or modulate disease severity. Because the inflammatory response in AS is characterized by the production of increased amounts of several proinflammatory cytokines at sites of disease, including TNF, IL-1. The aim to present study is to determine the di-allelic polymorphisms of IL-1, TNF-alpha—these polymorphic sites include promoter regions of IL-1B at positions-511 (C-T transition), and -31 (C-T transition), and IL-1RN variable number tandem repeats, and promoter regions of TNF alpha at positions-863(G-C)-and describe distribution of Allele frequency and Genotype frequencies of IL-1B-31,IL-1B-511 TNF-a-863. To evaluate the association between IL-1,TNF loci polymorphisms and increased risk of coronary heart diseases in subjects from Han population of Henan Province in China.MethodsSubjects were divided into two groups, 121 patients with Coronary heart disease (CHD)and 138 controls who to be have a health examination excluded cardiovascular diseases in the out-patient clinic were studied. All subjects were recruited by age, sex, CHD family history, and pathological diagnosis . None of these subjects had a history of systemic lupus erythematosus, diabetes mellitus, rheumatoid arthritis, or inflammatory bowel disease, the diagnosis of CHD was based on biochemistry examination and PTCA examinations. Polymorphisms in IL-1B that encodes IL-1βand IL-IRN that encodes IL-1 receptor antagonist were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Similarly, Polymorphisms in TNF-alpha encodes TNF-a was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results1. The Allele frequency and Genotype frequencies of IL-1B-31,IL-1B-511,TNF-a -863 were conformed to Hardy-Weinberg Equilibrium. So we can also think the samples mate at random and can represent the population better.2. IL-1B-511 alleles were C/C, C/T and T/T. The frequencies in cases werel7.4%, 41.3%, 41.3% and the frequencies in controls were22.5%. 50.0%, 27.5%. Contrast the genotype of C/C, IL-1B-511 T/T carriers were at an increase risk of gastric cancer with an odds ratio of 3.2 (95%CI:1.1-4.5)and IL-1B-511C/T carriers were at an increase risk of gastric cancer with an odds ratio of 1.2 (95%CI:0.5-2.1). And -511T association achieved significance at P=0.05 when we used multivariable logistic regression analysis for risks of CHD (P=0.009 OR=4.89 95%CI 1.51-15.89).3. The polymorphism of IL-1B-31 allele was C/C, C/T and T/T. The frequencies in cases were 36.4%, 44.6%, 19.8% and the frequencies in controls were 40.6%, 39.9%,19.5%. No significant differences were observed between cases and controls in C/C and C/T genotype.4. Five kinds of polymorphism of IL-1RN were found as I/I,I/II, I/III,I/IV,II/II. and the frequencies of I/I in cases were 81.0%. respectively. However, the frequencies in controls were 79.0%. No significant differences were observed between cases and controls in each genotype.5. TNF-a-863 alleles were C/C, C/A and A/A. The frequencies in cases were 75.2%, 24.0%, 0.8% and the frequencies in controls were 62.6%, 35.7%, 1.7%. Contrast the genotype of C/C, TNF-a-863 C/C carriers were at an increase risk of gastric cancer with an Odds ratio of 1.8(1.01-3.1)and TNF-a-863C/A carriers were at an increase risk of gastric cancer with an odds ratio of 2.1(1.2-4.4). No significant differences were observed between cases and controls in each genotype. And -863C association achieved significance at P=0.05 when we used multivariable logistic regression analysis for risks of CHD (P=0.003 OR=7.52 95%CI:2.68-18.71).6. We found the distribution of IL-1B-31 has no significant differences with the distribution in Japan, but significant differences with the distribution in Korea(P <0.05); similarly, the distribution of IL-1B-511 has no significant differences with the distribution in Xi'an city in China and Korea, but significant differences with the distribution in Japan, American, German et al.(P<0.05); the distribution of IL-1RN has no significant differences with the distribution in Hubei province in China, Korea, but significant differences with the distribution in Japan, England et al.(P<0.05); the distribution of TNF-a-863 has no significant differences with the distribution in Hubei province in China, Japan, et al, but significant differences with the distribution of Caucasian(P<0.05).Conclusions1. C/T of IL-1B-31,IL-1B-511 and I/I of IL-1RN and C/C of TNF-a-863 were the main genotype both in cases and controls in HeNan Province. The distributions of genotypes have significant differences in different races and areas.2. In Han population of Henan Province, the polymorphism of TNF-a-863C/C,C/A and IL-1B-511T/T alleles may be associated with the susceptibility of CHD. However, no evidence was found to support that the polymorphisms of IL-1RNand IL-lB-31 alleles had relationship with CHD.
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