The Clinical And Basic Research Of Gout

Background:With the shift of economy and lifestyle, the prevalence of gout is increasing. Gout has become a common chronic disease. At the aspect of etiology, people are realizing that genetic factor plays an important role in gout. Even though lots of loci on human genome has been found recently, but this is merely the tip of an iceberg. Considering the aspect of therapeutics, treatment adherence, an important evaluation marker in chronic disease, has a great influence on the prognosis. The non-adherence of gout patients is a major problem.Objective:1. To investigate treatment adherence of gout and its associated factors in Chinese patients.2. To determine the effect of treatment adherence on gout management.3. To test the effectiveness of intensive care for gout.4. To explore the genetic factors related to gout and HUA (Hyperuricemia) in a Zhuang family.Method:1. A structured survey was carried out by telephone interview in349patients recruited from Gout Clinic at Peking Union Medical College Hospital. The associated factors with treatment adherence were investigated by logistic regression models and semi-quantitative interview. Linear and logistic regression were performed to estimate the effect of treatment adherence on gout management.2. A single armed self-reflection pilot trial was conducted in Gout Clinic at Peking Union Medical College Hospital.68gout patients were recruited and received an intensive care that include education, lifestyle advice and follow-up. The treatment adherence and other outcome such as sUA (Serum Uric Acid) were evaluated.3. To explore the genetic factors related to gout in a Zhuang gout family, Medical history, physical examination and laboratory work-up were collected. Allele sharing examination and exon sequencing were conducted to exclude common causative gene. Exome sequencing were performed to investigate potential causative gene.Result:1. The proportion of dietary and medication adherence is44.2%and21.9%. The factors associated with dietary adherence include age>60, sUA>642umol/L and tophi. The factors associated with medication adherence include tophi, chronic kidney disease and observation time less than1year. During the interview, patients reported the reasons caused non-adherence, including quiescence after treatment (35.1%) and worrying about adverse effects (22.7%)2. The difference of serum uric acid decline between patients adhered and non-adhered to medication was134(87-181)umol/L. Patients adhered to medication was associated with increased odds of acute attack frequency decline (OR=7.362,95%CI2.120-25.567, p=0.002) and tophi improvement (OR=2.515,95%CI1.039-6.084, p=0.039), and it was also associated with decreased odds of new involved joints (OR=0.153,95%CI0.036-0.656, p=0.011).3. In the pilot study, the proportion of medication adherence and patients sUA<360umol/1increased from8.8%to40%and from10.9%to41.0%. After a3month follow up, the proportion of medication adherence increased from34.2%to53.3%.4. There are6gout patients among this Zhuang family of4generation,21members.9of12with blood sample developed HUA. UMOD was found to be shared in this family by allele sharing experiment, but exclude after exon sequencing. After the Exome sequencing, TGM-1(Transglutaminase-1) G114D was shared in gout and HUA patient. A SNP (Single Nucleotide Polymorphism), rs2231142located on ABCG2, was also found to be shared among all the gout patient.Conclusion:1. The non-adherence of gout is a serious problem. Elderly, poorly controlled, comorbidity and short observation time are associated with treatment adherence. Medication adherence shows a great influence on sUA and other outcome of gout. The intensive care based on clinics and telephone follow-up improved the medication adherence and sUA of gout patients.2. In the Zhuang gout family, TGM-1G114D mutation is a potentially causative gene. SNP rs2231142on ABCG2may have a synergistic effect on the development of gout among this family.