The Association Study between Gout and Polymorphisms in the Interleukin-6 and Tumor Necrosis Factor-α Genes

• Main Authors: Pei-Chien Tasi, 蔡佩倩
• Other Authors: none
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/12652637333520111750

碩士 === 高雄醫學大學 === 公共衛生學研究所碩士班 === 93 === Abstract Gout, a chronic inflammatory disease, has become increasingly common among Taiwanese people. The factors, such as uric acid, triglycerides, creatinine, continuous consumption of alcohol, and family history of gout were known to be associated with gout. However, these factors are still unable to explain the mechanism of its occurrence since some persons with hyperuricemia were free of gout. Gout is categorized as chronic inflammatory disease and the genes related to inflammation are Interleukin-6（IL-6）、Interleukin-8（IL-8）、Tumor necrosis factor-α（TNF-α）、Marcophage inflammatory protein 2 (MIP2)...etc. Therefore, two inflammation-related mediator factors, IL-6 and TNF-α, and their correlations with gout are explored in this research. A hospital-based age matched cross-sectional study was conducted from May, 2004 to February, 2005 in Kaohsiung. In total, 121 male gout patients and the control group consisted of 188 age-matched (± 3 year old) healthy males were recruited. PCR-RFLP and gene sequencing were performed to identify four single nucleotide polymorphism sites, including 174G→C, -373A(n)T(m), -572G→C, -597G→A in IL-6 gene and two sites -308 G→A , -863 C→A in TNF-α gene. Haplotype analysis was also used to investigate the correlation between haplotypes and gout, Individuals with TNF-α -863CC genotype were found to have higher probability of developing gout 9.23 times as those with TNF-α -863AA (95% CI= 1.97-43.19, p= 0.0012). Compared to individuals with TNF-α -308GG/-863CC composite genotype, those with TNF-α -308GG/-863AA composite genotype were 9.66 times as likely to have gout. In addition, the probability of individuals with TNF-α -308G/-863A allele (95% CI= 2.05-45.53) getting gout was 2.06 times as high as the one of those with TNF-α -308G/-863C allele. The result of this research revealed that the factor such as hyperuricemia (OR= 5.81), high creatinine (OR= 3.63), continuous consumption of alcohol (OR= 2.07), BMI over 26.4 (OR= 2.07), high concentration of IL-6 in blood (OR= 2.03) and carriers of TNF-α -863AA genotype (OR= 9.23) were correlated to gout. According to the adjustment of other risk factors by a logistic regression model, it was found that those who carried TNF-α -863AA genotype (aOR= 6.42, 95% CI= 1.05-39.14) and with hyperuricemia (aOR= 4.61, 95%CI= 2.55-8.35) contributed the most to the occurrence of gout, which increased the risk of having gout by factors of 6.42 and 4.61 respectively. Other factors including high creatinine (aOR= 2.96, 95% CI= 1.66-5.31), BMI over 26.4 (aOR= 2.83, 95% CI= 1.41-4.54 ), high concentration of IL-6 in blood (aOR= 1.92, 95% CI= 1.11-3.24 ), and continuous consuming of alcohol (aOR= 2.36, 95% CI= 1.12-4.97) also increased the risk of gout 2.96 times, 2.83 times, 1.92 times, and 2.36 times respectively. In conclusion, the well-known risk factors such as hyperuricemia, creatinine, continuous consumption of alcohol, BMI over 26.4 were confirmed to be associated with gout from the result of this research. In addition, the SNP site TNF-α C-863A and high IL-6 concentration in blood also had strong correlation with gout.