Clinical characteristics and risk factors for primary gout patients with multiple subcutaneous tophi / 中华内分泌代谢杂志

Objective:To investigate the clinical characteristics and risk factors of multiple tophi among gout patients.Methods:Gout patients treated at Affiliated Hospital of Qingdao University from September 2017 to September 2021 were included retrospectively. According to the number of tophi, the patients were divided into the multiple tophi group, the single tophi group and the non-tophi group. Clinical data were collected, biochemical indices and urine pH value were determined. One- way ANOVA or Chi-square test was used to compare groups, and multivariate logistic regression was used to analyze the risk factors. Results:The age, disease course, blood pressure, serum uric acid, urea nitrogen, and the rate of family history, smoking, drinking, gout attacks≥2 twice per year, hypertension, cardio-cerebrovascular diseases, kidney stones in the multiple tophi group were significantly higher than those in the single tophi group and the non-tophi group. The glomerular filtration rate, urine pH value and the rate of regular exercise were significantly lower than those of single tophi group and non-tophi group. In the multiple tophi group, 245 cases(44.46%) were involved in the interphalangeal joint or metacarpophalangeal joint, 212 cases(38.47%) were involved in other joints of the upper limb, which was second only to the first metatarsophalangeal joint(349 cases, 63.33%). Logistic regression analysis showed that the course of disease, urea nitrogen, serum uric acid, positive family history, drinking, gout attacks ≥twice per year and hypertension were the risk factors for multiple tophi in gout patients. Conclusion:Patients with a long disease course, elevated uric acid, high urea nitrogen, positive family history, alcohol consumption, frequent gout flare and hypertension are more likely to develop multiple tophi.

Clinical characteristics and risk factors for young primary gout patients with subcutaneous tophi / 中华风湿病学杂志

Objective:To analyze the clinical characteristics and risk factors associated with the formation of subcutaneous tophi among young gout patients.Methods:Gout patients treated at the Affiliated Hospital of Qingdao University from September 2016 to June 2020 were included. The clinical information was collected and relevant biochemical indices were detected. Fasting urine was collected to test urine pH value, urine uric acid and urine creatinine. Patients were divided into young tophi group and non-tophi group according to age. The measurement data of normal distribution was expressed as Mean±Standard deviation, and independent sample t test and one-way analysis of variance were used. The counting data was tested by Chi-square test. The risk factors were analyzed by logistic regression. Results:A total of 4 798 primary gout patients were collected. There were 915 patients with subcutaneous tophi, 2 308 young gout patients, 252 young gouty tophi patients among them. The average BMI, waist circumference, hip circumference, triglyceride level, serum uric acid level, glomerular filtration rate, alanineamino -transferase (ALT) and aspartate amino -transferase (AST) in the young tophi group were significantly higher than those in the middle-age tophi group ( F=46.074, 2.551, 9.203, 10.370, 15.118, 68.741, 35.023, 5.175, all P<0.05). Average age of disease onset, systolic blood pressure, fasting blood glucose, urine FEUA, Uua/Ucr and urea nitrogen level in young tophi group were significantly lower than those in middle-age tophi group ( F=474.876, 7.629, 6.441, 34.877, 3.633, 50.867, all P<0.05]. The age [(35±7) years old vs (33±7) years old], disease course [(7±4) years vs (4±3) years], blood pressure [(139±17) mmHg vs (135±16) mmHg], [(90±13) mmHg vs (86±12) mmHg], serum triglyceride [(2.6±2.1) mmol/L vs (2.4±2.0) mmol/L], total cholesterol [(4.9±1.4) mmol/L vs (4.6±1.4) mmol/L], serum uric acid [(547±171) μmol/L vs (490±160) μmol/L], urea nitrogen [(5.0±2.0) mmol/L vs (4.4±1.7) mmol/L], family history (27.0% vs 19.6%) and smoking rate(56.0% vs 48.9%) of tophi patients were significantly higher than those of non-tophi patients in young patients ( t=4.717, P<0.05; t=12.838, P<0.05; t=3.414, P<0.05; t=4.676, P<0.05; t=2.085, P<0.05; t=2.451, P<0.05; t=5.308, P<0.05; t=4.090, P<0.05; χ2=7.423, P<0.05; χ2=4.235, P<0.05) . The age of disease onset [(28±6) years vs (29±7) years] and glomerular filtration rate [(96±21) ml·min -1·1.73 m -2vs (103±21) ml·min -1·1.73 m -2] were statistically significantly lower than those of non-tophi patients ( t=-2.711, P<0.01; t=-4.907, P<0.01). Logistics regression analysis showed that age, course of disease, blood pressure, blood lipids level, serum uric acid level, family history of gout and smoking were risk factors for the formation of tophi in young people. After further adjusted for age, course of disease and family history of gout, it was found that serum uric acid, systolic blood pressure, diastolic blood pressure and urea nitrogen remined risk factors for tophi, while glomerular filtration rate remained a protective factor in young patients. Conclusion:Young tophi patients are always obese and have lipid metabolism disorder. Young patients with high level of serum uric acid and blood pressure, decreased renal function are prone to complicate with subcutaneous tophi. More attention should be paid in clinical practice to prevent or delay the formation of tophi.

A whole genome sequencing result and preliminary analysis of a primary gout pedigree / 中华内分泌代谢杂志

Objective:To screen gene mutation information of gout pedigree through whole genome sequencing and to carry out preliminary analysis.Methods:One typical gout pedigree was selected as the study subjects. The clinical data and the peripheral blood samples were collected and constructed charts of the pedigree. DNAs were extracted from peripheral blood and analyzed by the whole genome sequencing, and by the software analysis and comparison, screening out the pathogenic genes and related mutations. Then the verifications were conducted in the family members and the controls. Bioinformatics software was applied to predict the effect of mutation on gene expression.Results:Based on the sequencing results, advanced informational analysis was performed to screen out the mutations 1040-8 A> G near the 5 ′end near the exon 8 of the PLAA gene. The results showed that all the gout patients in the family had 1040 -8 A> G sites, and none of the mutants were found in the non-gout group and 200 controls; bioinformatics analysis suggested that the mutation could affect PLAA gene expression, but not affecting PLAA mRNA structure.Conclusion:PLAA gene 1040-8 A> G mutation is separated from patients in the gout pedigree, and the newly discovered PLAA gene may act as a gout pathogenic gene.

Analysis of risk factors for susceptibility of abnormal liver function in male patients with gout / 中华内分泌代谢杂志

Objective:To investigate the risk factors for susceptibility of abnormal liver function in patients with gout.Methods:A total of 5 044 cases of male gout patients in remission were selected and divided into normal liver function group with 3 693 patients and abnormal liver function group with 1 351 patients. The clinical information was collected and relevant biochemical indices were detected. Serum uric acid(SUA) was divided into quartiles, and its associations with elevated ALT were evaluated.Results:There were significant differences in the history of drinking, family history, combining with hyperlipidemia, fatty liver, and coronary heart disease between the abnormal liver function group and normal function group( P<0.05 or P<0.01). There were significant statistical differences in age, disease duration, body mass index, waist circumference, diastolic blood pressure, serum cholesterol and triglyceride, uric acid, and creatinine clearance rate between 2 groups( P<0.01), while without significant difference in history of smoking, regular exercise, combining hypertension and diabetes, the means of systolic blood pressure, and fasting blood glucose(all P>0.05). Further logistic regression analysis indicated that body mass, waist circumference, combining fatty liver, higher SUA level, higher cholesterol and triglyceride were risk factors of the early onset of abnormal liver function. ALT and the proportion of abnormal liver function were increased with the increase of UA. After adjustment for BMI, TG, TC and fatty liver, the ALT level and the proportion of abnormal liver function decreased significantly while still showed an upward trend. Conclusion:Patients with obesity, high level of uric acid, high blood lipids and fatty liver were more likely to develop abnormal liver function, SUA was independently associated with elevated ALT.

Analysis of the therapeutic effect and influencing factors of alkalized urine in patients with gout / 中华内分泌代谢杂志

Objective:To investigate the therapeutic effect and influencing factors of alkalized urine in patients with gout, thus providing the basis for the clinical treatmeat.Methods:A total of 90 cases of gout patients in remission without alkalization of urine and lowering uric acid treatment were selected from January 2019 to June 2019. All patients were given a low purine diet (purine intake<200 mg/d). 90 patients were randomly divided into different drugs of alkalized urine groups according to rardom number table: sodium bicarbonate group, taking potassium sodium hydrogen citrate 1.0 g tid; the citrate granule group, taking potassium sodium hydrogen citrate 2.5 g tid; and control group, taking low purine diet only. On the 5th day of treatment, fasting urine in the morning was retained, breakfast was prescribed, and alkalized urine drugs were taken after the meal. Their urine pH was determined at 1 h, 2 h, 3 h, and 4 h after the medicine taken, and copmare the changes of urine pH in different groups. Taking urine pH 6.2 as cut-off point, patients receiving alkalized urine drugs were divided into the standard group (urine pH≥6.2) and the non-standard group (urine pH<6.2) according to their mean urine pH at 2 h, 3 h, and 4 h after taking medicine. Finally, the influencing factors of urine pH were compared between the groups.Results:There were no significant differences in fasting urine pH between the sodium bicarbonate group and the control group, but the urine pH of 2 h and 3 h after sodium bicarbonate taken were significantly higher than the control group ( P<0.05). The urine pH of the citrate granule group was higher than the control group and the sodium bicarbonate group on fasting and at any time after taking drugs ( P<0.05 or P<0.01). The peak pH value of urine in the sodium bicarbonate and citrate granule groups was 4 h after taking drugs, followed by 2 h and 3 h. There were statistically significant differences in body mass index, waist circumference, and blood pressure between the standard and non-standard groups ( P<0.05 or P<0.01). Conclusion:Fasting urine pH alone can not be used as an index for the efficacy of alkalized urine, it is recommended to refer to the pH value of 2-4 h after taking drugs. The efficacy of potassium sodium hydrogen citrate was better than that of sodium bicarbonate. Obesity or overweight seems to be an adverse factor affecting the alkalized urine.

Research progress on risk factors of tophus formation / 中华全科医师杂志

Tophus is the sign of chronic gout, which can lead to bone destruction, joint dysfunction, and significantly increase the risk of cardiovascular disease and death. Tophus has a structure of chronic foreign body granuloma,and extracellular reticular trap of neutrophils may be the main mechanism for the formation of tophi. Several factors can lead to the tophus formation. This article reviews the recent advances in the study of biology,risk factors and therapy of tophus.

Analysis of risk factors for susceptibility of abnormal liver function in male patients with gout / 中华内分泌代谢杂志

Objective@#To investigate the risk factors for susceptibility of abnormal liver function in patients with gout.@*Methods@#A total of 5 044 cases of male gout patients in remission were selected and divided into normal liver function group with 3 693 patients and abnormal liver function group with 1 351 patients. The clinical information was collected and relevant biochemical indices were detected. Serum uric acid(SUA) was divided into quartiles, and its associations with elevated ALT were evaluated.@*Results@#There were significant differences in the history of drinking, family history, combining with hyperlipidemia, fatty liver, and coronary heart disease between the abnormal liver function group and normal function group(P<0.05 or P<0.01). There were significant statistical differences in age, disease duration, body mass index, waist circumference, diastolic blood pressure, serum cholesterol and triglyceride, uric acid, and creatinine clearance rate between 2 groups(P<0.01), while without significant difference in history of smoking, regular exercise, combining hypertension and diabetes, the means of systolic blood pressure, and fasting blood glucose(all P>0.05). Further logistic regression analysis indicated that body mass, waist circumference, combining fatty liver, higher SUA level, higher cholesterol and triglyceride were risk factors of the early onset of abnormal liver function. ALT and the proportion of abnormal liver function were increased with the increase of UA. After adjustment for BMI, TG, TC and fatty liver, the ALT level and the proportion of abnormal liver function decreased significantly while still showed an upward trend.@*Conclusion@#Patients with obesity, high level of uric acid, high blood lipids and fatty liver were more likely to develop abnormal liver function, SUA was independently associated with elevated ALT.

A whole genome sequencing result and preliminary analysis of a primary gout pedigree / 中华内分泌代谢杂志

Objective@#To screen gene mutation information of gout pedigree through whole genome sequencing and to carry out preliminary analysis.@*Methods@#One typical gout pedigree was selected as the study subjects. The clinical data and the peripheral blood samples were collected and constructed charts of the pedigree. DNAs were extracted from peripheral blood and analyzed by the whole genome sequencing, and by the software analysis and comparison, screening out the pathogenic genes and related mutations. Then the verifications were conducted in the family members and the controls. Bioinformatics software was applied to predict the effect of mutation on gene expression.@*Results@#Based on the sequencing results, advanced informational analysis was performed to screen out the mutations 1040-8 A> G near the 5 ′end near the exon 8 of the PLAA gene. The results showed that all the gout patients in the family had 1040 -8 A> G sites, and none of the mutants were found in the non-gout group and 200 controls; bioinformatics analysis suggested that the mutation could affect PLAA gene expression, but not affecting PLAA mRNA structure.@*Conclusion@#PLAA gene 1040-8 A> G mutation is separated from patients in the gout pedigree, and the newly discovered PLAA gene may act as a gout pathogenic gene.

Clinical characteristics in gout patients with different body mass index / 中华内科杂志

Objective Obesity is one of the risk factors for gout.The aim of the present study was to evaluate clinical characteristics of gout patients with different BMI.Methods A total of 5 104 patients with gout were enrolled and divided into three groups according to the BMI.The clinical information was collected and relevant biochemical indices were detected.SPSS software was applied for the statistical analyses.Results There were significant differences in the ratios of gender,regular exercise,hypertension,tophus,renal insufficiency,hyperlipidemia,impaired glucose metabolism,liver dysfunction among the three groups (all P＜0.01).The onset age in overweight [45(36,55) years] and obese subjects [40(31,50)years] were earlier than that of the normal weight subjects [50 (38,61) years].Moreover,waist circumstances [103(99,108) cm and 94 (90,98) cm vs 87 (82,91) cm],systolic pressure [130 (120,145) mmHg (1 mmHg =0.133 kPa) and 130 (120,140) mmHg vs 128 (115,140) mmHg],diastolic pressure [90 (80,100) mmHg and 85 (80,92) mmHg vs 80 (79,90) mmHg],fasting blood glucose [5.77 (5.30,6.44) mmol/L and 5.65 (5.19,6.26) mmol/L vs 5.55 (5.10,6.15) mmol/L],TG [2.10 (1.46,3.04) mmol/L and1.88 (1.35,2.78) mmol/L vs 1.52 (1.07,2.39) mmol/L],TC [5.20 (4.55,5.93) mmol/L and 5.07 (4.46,5.75) mmol/L vs 4.95 (4.27,5.65) mmol/L],serum uric acid [483(418,552) μmol/L and461(395,524) μmol/L vs440 (368,517) μmol/L],ALT [30 (21,46) U/L and25 (18,36) U/L vs 21 (14,29) U/L],AST [21(17,28) U/L and 20 (17,26) U/L vs 20 (6,25) U/L],the number of joints involved [2 (1,3) joints and 2 (1,2) joints vs 1 (1,2) joints] in the overweight and obese groups were higher than those in the normal weight group (all P ＜ 0.01).There were no statistical differences in family history,involvement of upper limb joints,kidney stones and coronary heart disease among the three groups (all P ＞ 0.05).Conclusions Obesity is associated with an earlier age of gout onset.With the increase of BMI,the blood pressures,glucose,lipid,serum uric acid,liver transaminase levels and the number of involved joints increased gradually.Cautions should be taken in treating patients with different BMI.

Analysis of risk factors for susceptibility of subcutaneous tophi in people with gout / 中华内分泌代谢杂志

Objective To discuss the risk factors for susceptibility of subcutaneous tophi with an aim to provide clinical evidence for the prevention and treatment of tophi.Methods A total of 5 321 cases of gout patients whose course of disease was less than 10 years were selected and divided into two groups according to whether a subcutaneous tophus was present. The clinical information was collected and relevant biochemical indices were detected.Results There were significant differences in the ratios of regular exercise, involvement of upper limb joints, combining renal insufficiency, kidney stone and coronary heart disease between the tophus group and the non-tophus group(P0.05). Further logistic regression analysis indicated that disease duration, a large number of joints involved, the involvement of upper limb joints, combining kidney stones, higher serum uric acid level, and higher diastolic pressure were risk factors of the early onset of subcutaneous tophi, while regular exercise and body mass index were protective factors.Conclusion Patients with long duration, high serum level of uric acid, a large number of joints involved, upper limb joint involved, kidney stones, and hypertension were more likely to develop subcutaneous tophi. These risk factors should be intervened actively in clinic.

Association of single nucleotide polymorphisms of susceptibility genes of type 2 diabetes mellitus with liability to gout among ethnic Han Chinese males from coastal region of Shandong / 中华医学遗传学杂志

OBJECTIVE To assess the association of single nucleotide polymorphisms (SNPs) of susceptibility genes of type 2 diabetes mellitus (T2DM) with liability to gout among ethnic Han Chinese males from coastal region of Shandong province. METHODS Seven SNPs within the susceptibility genes of T2DM, including rs10773971(G/C) and rs4766398(G/C) of WNT5B gene, rs10225163(G/C) of JAZF1 gene, rs2069590(T/A) of BDKRB2 gene, rs5745709(G/A) of HGF gene, rs1991914(C/A) of OTOP1 gene and rs2236479(G/A) of COL18A1 gene, were typed with a custom-made Illumina GoldenGate Genotyping assay in 480 male patients with gout and 480 male controls. Potential association was assessed with the chi-square test. RESULTS No significant difference was detected for the 7 selected SNPs in terms of genotypic and allelic frequencies (P > 0.05). When age and body mass index (BMI) were adjusted, the 7 genetic variants still showed no significant association with gout. CONCLUSION The genotypes of the 7 selected SNPs are not associated with gout in ethnic Han Chinese male patients from the coastal region of Shandong province. However, the results need to be replicated in larger sets of patients collected from other regions and populations.

Association of single nucleotide polymorphisms of cytochrome P450 gene with susceptibility to gout in ethnic Han males from coastal regions of Shandong province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of cytochrome P450 gene single nucleotide polymorphisms (SNPs) with susceptibility to gout in ethnic Han males from coastal regions of Shandong province.</p><p><b>METHODS</b>Four hundred and eighty male patients with gout and 480 healthy male controls were included. Genotyping was carried out with a custom Illumina GoldenGate Genotyping assay to detect SNP rs2275620 of CYP2C8 gene, SNP rs2070676 of CYP2E1 gene, SNP rs837395 of CYP4B1 gene, and SNP rs194150 of TBXAS1 gene. The association was assessed with chi-square test.</p><p><b>RESULTS</b>No significant difference has been found between the two groups in regard to the genotypic and allelic frequencies of the TT, AT, AA genotypes and A, T alleles of the SNP rs2275620 of the CYP2C8 gene (P=0.88; P=0.97), the CC, CG, GG genotypes and C,G alleles of SNP rs2070676 of the CYP2E1 gene (P=0.24; P=0.09), the TT, AT, AA genotypes and A, T alleles of SNP rs837395 of the CYP4B1 (P=0.88; P=0.97), and TT, AT, AA genotypes and the A,T alleles of SNP rs194150 of TBXAS1 gene (P=0.15; P=0.06).</p><p><b>CONCLUSION</b>This study has identified no association of SNP loci rs2275620(A/T) of CYP2C8, rs2070676(C/G) of CYP2E1, rs837395(A/T) of CYP4B1 and rs194150(A/T) of TBXAS1 with gout in ethnic Han males from coastal regions in Shandong province. However, our result needs to be replicated in larger sets of patients collected from other regions and populations.</p>

Relationship between interleukin-1β -31C/T polymorphism and susceptibility to gout in Chinese male population / 中华风湿病学杂志

Objective To explore gene polymorphism of the C/T genotype of rs1143627 in the promoter of IL-1β gene in male population living in the coastal area of Shandong, and thus to investigate the relationship between the gene polymorphism of IL-1β and gout. Methods A total of 208 gout patients and 210 healthy controls were enrolled. The possible association between the polymorphism of IL-1 β -3 1C/T and gout in Chinese were investigated and genotype frequencies and allelic frequencies was calculated by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Hardy-Weinberg was used to verify the representativeness of the sample. Comparisons between the groups were performed with χ2 test and t-test. Results The frequencies of CC, CT, and TT genotypes were 32.7%, 43.3% and 24.0%,respectively among gout patients, while they were 31.9%,46.2% and 21.9%, respectively among the controls.There was no statistically difference in IL-1β -31C/T genotype frequencies between gout patients and controls (χ2=0.427, P>0.05). The allele frequencies of C and T in gout cases were different from those in the controls (54.3%, 55.0%; 45.7%, 45.0%; χ2=0.038, P>0.05). Moreover, no association between IL- I β-31 C/T genotypes and risk factors for gout were observed in gout cases by χ2 test. Conclusion Results of the present study suggest that the C/T genotype of rs1143627 in the promoter of IL-1β gene is not associated with gout in male population living in the coastal area of Shandong.

The association between single-nucleotide polymorphisms of hURAT1 and hyperuricemia in Han Chinese / 中华内科杂志

Objective To study the association between hURAT1 gene single nucleotide polymorphism(SNP) and primary hyperuricemia(HUA). Methods A total of 215 patients with HUA and 323 healthy subjects were chosen to investigate SNP of hURAT1. Exon 2 to 4 and flanking introns of the hURAT1 gene in patients and control individuals were screened with PCR. The relationship between SNP of hURAT1 gene with HUA was studied with statistical analysis. Results The frequency of AA/AG genotype was significantly increased in HUA patients as compared with that in healthy controls( 11.6% vs 3.7% ,P =3.81 × 10-4). Allele A of hURAT1 intron 3, 11 G ＞A was found significantly higher in the group of HUA patients, being detected in 6.0% of the HUA patients alleles and in 1.9% of the healthy control alleles (P =2.66 × 10-5 ). Those carrying the low frequency AA/AG genotype had a risk effect on the morbidity of HUA and the odds ratio for the HUA patients versus controls was 3.41 with AA/AG genotype versus GG genotype( OR = 3.41,95% CI = 1.67 - 6.95 ). The HT4 haplotype, which carried the intron 3,11A allele, was associated with a significantly increased risk of HUA(69.44% vs 30.56% ,P ＜ 0.001). Conclusion The SNP of 11G ＞A in the intron 3 of hURAT1 gene was apparently associated with HUA, thus suggesting the genetic effect of hURAT1 gene in the pathogenesis of HUA.

Promoter methylation status and protein expression of p14ARF gene in squamous cell carcinoma and adenocarcinoma of the lung / 中国肺癌杂志

<p><b>BACKGROUND</b>Recently, the p14 ARF gene has emerged as a new putative tumor suppressor gene, and the alteration of p14 ARF gene is closely related to development of multiple human tumors. The aberrant promoter methylation as a mechanism of inactivation of p14 ARF gene might participate in tumorigenesis. The aim of this study is to investigate promoter methylation status and protein expression of p14 ARF gene in pulmonary squamous cell carcinoma and adenocarcinoma, and to value the role of p14 ARF promoter methylation in carcinogenesis of non-small cell lung cancer.</p><p><b>METHODS</b>Promoter methylation status and protein expression of p14 ARF gene were analyzed in 40 cases of pulmonary squamous cell carcinoma and adenocarcinoma by methylation specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR) and immunohistochemistry (IHC).</p><p><b>RESULTS</b>The positive rate of p14 ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer was 17.5% (7/40) and 2.5% (1/40) respectively (P= 0.025 ). The results of RE-PCR were consistent with the above. The positive rate of p14 ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer (P=0.003). Promoter methylation and protein expression of p14 ARF gene showed a significantly negative correlation (r=-0.56, P= 0.001 ), and both of them did not correlate statistically with the clinicopathologic characteristics of patients such as histological classification, TNM stages, differentiation grade and lymph node involvement.</p><p><b>CONCLUSIONS</b>Promoter methylation is a crucial mechanism of inactivation of p14 ARF gene. Promoter methylation of p14 ARF gene might be involved in carcinogenesis of non-small cell lung cancer, and it is an early event in development process of non-small cell lung cancer.</p>