Association of tumor necrosis factor-alpha gene of G-308A genotype and mRNA expression with serum uric acid in hyperuricemic patients / 中国组织工程研究

ABSTRACT

BACKGROUND: Hyperuricemia (HUA), serving as a component of metabolic syndromes (MS), has a major regulatory role in inflammatory responses. However, the correlation between G-308A tumor necrosis factor-α (TNF-α) and MS is still controversial.OBJECTIVE: To study the correlation among G-308A TNF-α genotype distribution, TNF-α mRNA expression and C-reactive protein (CRP) in patients with HUA.DESrGN Patients with HUA were selected as the subjects, while normal peoplewere taken as the controls.SETTING: Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology.PARTICIPANTS: Subjects were selected from 5 003 people, including 188 patients with HUA and 51 healthy people.Patients with HUA included 40 patients with simple HUA, 42 patients with HUA and dyslipidemia, 80 patients with HUA and dyslipidemia and hypertension, and 26 patients with gout (administration of allopurinol was stopped at one week before the experiment).METHODS: TNF-α gene promoter G-308A genotype was determined by using PCR application followed by Nco/digestion.TNF-α mRNA expression was studied by RT-PCR with semi-quantitative analysis. Antibody sandwich method and enzyme linked immunosorbent assay (ELISA) were adopted to determine the CRP concentration. And the serum uric acid was measured by uricase method, while the insulin resistance index (IRI) was evaluated with homeostasis model.MArN OUTCOME MEASURES: ① Hardy-Weinberg equilibrium test of genotypic frequency. ② Changes in distribution of G-308A TNF-α genotypes and TNF-α mRNA expression in patients with HUA. ③ Changes in TNF-α mRNA expression and other parameters in G-308A TNF-α AA+GA and GG groups. ④ Multiple stepwise regression analysis.RESULTS: A total of 188 patients and 51 normal people were involved in the analysis of results. ① G-308A TNF-α genotypes distribution in 239 enrolled subjects accorded with Hardy-Weinberg equilibrium. ② AA+GA was compared with GG due to lower frequency of AA in population. The results revealed the HUA with dyslipidemia and hypertension group displayed a greater prevalence in G-308A TNF-α AA+GA genotype (30%) than that in the control group (12%) (P ＜ 0.05),while there were no significant differences among other groups. ③ TNF-α mRNA expression and CRP concentration were the highest in the gout group, and HUA accompanied by dyslipidemia and hypertension group listed the second,and then was the HUA and dyslipidemia group, while simple HUA group listed the last, all of which were higher than those in the normal control group (P ＜ 0.05-0.01). TNF-α mRNA expression in HUA accompanied by dyslipidemia and hypertension group, gout group was higher than that in the normal control group (P ＜ 0.05-0.01). The WHR, SBP, DBP,serum uric acid, triglycerides, TNF-α mRNA expression and CRP concentration in AA+GA group were remarkably higher than those in the GG group (P ＜ 0.05-0.01). ④ After adjustment of age, gender, systolic pressure, diastolic pressure,fasting blood glucose, and multiple variable linear stepwise regression showed that triglycerides, uric acid, TNF-α 308 A carrier were related with quantityof TNF-α mRNA expression. Meanwhile, the uric acid concentration, WHR and the quantity expression of TNF-α were significantly in positive association with CRP concentration.CONCLUSTONThe genotype of TNF-α 308 A carriers is associated with TNF-α expression and plasma CRP levels in HUA patients.