Chia-Chun Tseng

Reduced incidence of Type 1 diabetes and Type 2 diabetes in systemic sclerosis: A nationwide cohort study.

OBJECTIVES The purpose of this study is to investigate whether systemic sclerosis is a risk factor for diabetes. METHODS From Taiwans National Health Insurance Research Database and Registry of Catastrophic Illness database, we enrolled patients with systemic sclerosis and controls. Each systemic sclerosis patient was matched to at most three controls by sex, age, month and year of first diagnosis. Standardized incidence ratio (SIR) of diabetes in systemic sclerosis patients, and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). RESULTS A total of 2671 patients with systemic sclerosis and 7769 controls were enrolled. Patients with systemic sclerosis had decreased type 1 diabetes (SIR: 0.18, 95% CI=0.04-0.82). In female groups, systemic sclerosis patients also had lower rates of incident type 1 diabetes (SIR: 0.21, 95% CI=0.05-0.95). Male and female patients with systemic sclerosis both had lower rates of incident type 2 diabetes (SIR: 0.46, 95% CI=0.29-0.72; SIR: 0.41, 95% CI=0.33-0.51, respectively). Systemic sclerosis patients had decreased type 1 diabetes and type 2 diabetes (HR: 0.18, 95% CI=0.04-0.74; HR: 0.42, 95% CI=0.36-0.50, respectively) after adjusting for age and sex. CONCLUSIONS The results clearly showed that patients with systemic sclerosis had lower incidence of type 1 diabetes and type 2 diabetes compared to control subjects.

Increased Cumulative Incidence of Dermatomyositis in Ulcerative Colitis: a Nationwide Cohort Study.

On a molecular level, two autoimmune diseases: ulcerative colitis (UC) and dermatomyositis share common genetic determinants. On a clinical level, case reports evidenced the co-occurrence of these two diseases. We therefore hypothesize that UC is potentially associated with increased cumulative incidence of dermatomyositis. The goals of this retrospective cohort study were to evaluate whether UC is associated with increased cumulative incidence of dermatomyositis independent of sex and age. For comparison, we also assessed the cumulative incidence of polymyositis in UC and control subjects. The study enrolled 3,133 UC subjects and 14,726 control subjects. The cumulative incidence of dermatomyositis was significantly higher in UC than that of control subjects (p = 0.026), but the cumulative incidence of polymyositis was comparable between UC and control subjects (p = 0.596). UC was independently associated with the increased incident dermatomyositis (hazard ratio: 6.19, 95% confidence interval = 1.77–21.59, p = 0.004) after adjusting for sex, age, and concomitant rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. Similar trends of increased dermatomyositis in UC were observed when patients were stratified based on sex and age. In conclusion, our findings suggest that UC is probably associated with increased cumulative incidence of dermatomyositis, independent of sex, age, and concomitant autoimmune diseases.

Sex differential association of dermatomyositis with Sjögren syndrome

BACKGROUND: Although dermatomyositis and Sjögren syndrome share serologic autoantibodies and genetic polymorphisms, population data about the incidence of Sjögren syndrome in patients with dermatomyositis is unavailable. We performed a nationwide cohort study to explore the potential relation between dermatomyositis and Sjögren syndrome and, if an association exists, to elucidate whether it varies by sex. METHODS: We identified all patients with newly diagnosed dermatomyositis from the Registry of Catastrophic Illness Database in Taiwan between Jan. 1, 1998, and Dec. 31, 2011. Each patient was matched to, at most, 5 control patients from the National Health Insurance Research Database by age, sex and entry date. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of Sjögren syndrome after adjusting for age, sex, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. RESULTS: A total of 1602 patients with dermatomyositis and 7981 control patients were enrolled in the study. There was a positive association of having Sjögren syndrome among patients with dermatomyositis after adjusting for age, sex, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis (HR 2.67, 95% CI 2.01–3.54). The association was more pronounced in the male cohort (HR 2.69, 95% CI 1.19–6.09). INTERPRETATION: We found a sex differential association of Sjögren syndrome among patients with dermatomyositis independent of age and concomitant autoimmune disease. Further studies are required to determine the clinical importance of this association for both outcomes and therapeutic options.

Increased incidence of Sjogren's syndrome in systemic sclerosis: A nationwide population study.

Abstract In the past, there were no studies to evaluate the incidence of Sjogren’s syndrome and its relationship with sex and age in patients with systemic sclerosis. In this study, we enrolled 2217 patients with systemic sclerosis and 6485 controls from Taiwan’s Registry of Catastrophic Illness database and National Health Insurance Research Database. Every patient with systemic sclerosis was matched to at most three controls by sex, age, month, and year of first diagnosis of systemic sclerosis. Standardized incidence ratio (SIR) of Sjogren’s syndrome in patients with systemic sclerosis and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). Both male and female patients with systemic sclerosis had higher incidences of Sjogren’s syndrome (SIR: 7.59, 95% CI = 2.97–19.51; SIR: 7.59, 95% CI = 5.56–10.42, respectively). The incidence of Sjogren’s syndrome in patients with systemic sclerosis was still higher compared with control when stratified according to age. Age at diagnosis of Sjogren’s syndrome was earlier in patients with systemic sclerosis in both male and female groups (p = 0.018; p < 0.001, respectively). Systemic sclerosis was associated with Sjogren’s syndrome after adjusting for age, sex, and various autoimmune diseases (HR: 5.98, 95% CI = 4.79–7.47, p < 0.001). Common cytokines, overlapping antibodies, and similar risk alleles were all potential causes of increased incidence of Sjogren’s syndrome in systemic sclerosis.

ABCG2 contributes to the development of gout and hyperuricemia in a genome-wide association study

Although many genome-wide association studies (GWASs) of hyperuricemia or gout have been reported, the related genetic factors and the mechanisms from hyperuricemia to gouty attack remain unclear. This study aimed to identify genetic factors and pathogenesis of gout from hyperuricemia by genome-wide association study (GWAS). 747 gout patients, 747 hyperuricemia and 2071 age-matched controls were recruited and analyzed with Affymetrix 650 K chip to find the related genetic variants. The functions of the related genes were investigated in an endothelial cell (EC) with urate crystal stimulation. The GWAS results showed 36 SNPs to be strongly associated with gout compared to controls (all p-values < 10−7). Whereas the rs2231142 in ABCG2 gene had significant associations between gout and controls, between gout and hyperuricemia, and between hyperuricemia and controls (all p-values < 10−7), and the ORs were 4.34, 3.37 and 2.15 (all p-values < 0.001) after adjustment of potential confounders, respectively. The cell model showed significantly higher IL-8 release from EC combined with ABCG2 knockdown. We concluded that ABCG2 gene contributed to hyperuricemia but also gout, and that it was involved in the inflammation dysregulation via augmented IL-8 release in EC.

Next-generation sequencing profiling of mitochondrial genomes in gout

BackgroundAccumulating evidence implicates mitochondrial DNA (mtDNA) alleles, which are independent of the nuclear genome, in disease, especially in human metabolic diseases. However, this area of investigation has lagged behind in researching the nuclear alleles in complex traits, for example, in gout.MethodsNext-generation sequencing was utilized to investigate the relationship between mtDNA alleles and phenotypic variations in 52 male patients with gout and 104 age-matched male non-gout controls from the Taiwan Biobank whole-genome sequencing samples. Differences from a reference sequence (GRCh38) were identified. The sequence kernel association test (SKAT) was applied to identify gout-associated alleles in mitochondrial genes. The tools Polymorphism Phenotyping, Sorting Intolerant From Tolerant (SIFT), Predict the pathology of Mutations (PMUT), Human Mitochondrial Genome Database (mtDB), Multiple Alignment using Fast Fourier Transform (MAFFT), and Mammalian Mitochondrial tRNA Genes (Mamit-tRNA) were used to evaluate pathogenicity of alleles. Validation of selected alleles by quantitative polymerase chain reaction of single nucleotide polymorphisms (qPCR SNPs) was also performed.ResultsWe identified 456 alleles in patients with gout and 640 alleles in non-gout controls with 274 alleles shared by both. Mitochondrial genes were associated with gout, with MT-CO3, MT-TA, MT-TC, and MT-TT containing potentially pathogenic gout-associated alleles and displaying evidence of gene-gene interactions. All heteroplasmy levels of potentially pathogenic alleles exceeded metabolic thresholds for pathogenicity. Validation assays confirmed the next-generation sequencing results of selected alleles. Among them, potentially pathogenic MT-CO3 alleles correlated with high-density lipoprotein (HDL) levels (P = 0.034).ConclusionThis study provided two scientific insights. First, this was the most extensive mitochondrial genomic profiling associated with gout. Second, our results supported the roles of mitochondria in gout and HDL, and this comprehensive analysis framework can be applied to other diseases in which mitochondrial dysfunction has been implicated.

Increased Incidence of Amyotrophic Lateral Sclerosis in Polymyositis: A Nationwide Cohort Study

Past studies have shown common pathologic characteristics and shared immunologic features between polymyositis (PM) and amyotrophic lateral sclerosis (ALS). To explore the potential relationship between the 2 diseases, we performed a nationwide cohort study.

Increased incidence of multiple sclerosis in systemic sclerosis: A nationwide cohort study

OBJECTIVE Previous studies showed inconsistent results on the association of systemic sclerosis (SSc) with multiple sclerosis (MS), and are limited by a lack of adjustment for sex and age. The goals of this retrospective cohort study were to evaluate whether SSc is associated with increased incident MS independent of sex and age. METHODS We enrolled patients with SSc from Taiwans Registry of Catastrophic Illness Database and referent subjects from the National Health Insurance Research Database. Each SSc patient was matched to at most three referent subjects by sex, age, month and year of initial diagnosis of SSc. Incidence of MS in SSc patients and corresponding 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR) of MS. RESULTS The study enrolled 1171 patients with SSc and 3409 referent subjects. Patients with SSc had higher incidence of MS than referent subjects (9.35 per 1000 person-years, 95% CI=6.86-11.85; 0.13 per 1000 person-years, 95% CI=0.03-0.37, respectively). Similar results also occurred in both men and women. SSc was associated with increased incidence of MS after adjusting for sex and age (HR: 69.48, 95% CI=21.69-222.54). CONCLUSION SSc is associated with increased incidence of MS, independent of sex and age of the patients. Multidisciplinary teams should guide the assessment, treatment, and holistic care of SSc patients to reduce its morbidity.

Increased incidence of rheumatoid arthritis in multiple sclerosis: A nationwide cohort study.

AbstractPast studies have shown inconsistent results on whether there is an association between multiple sclerosis (MS) and rheumatoid arthritis. To investigate the possible relationship between the 2 autoimmune diseases, we performed a nationwide cohort study utilizing the National Health Insurance Research Database and the Registry of Catastrophic Illness.A total of 1456 newly diagnosed patients with MS and 10,362 control patients were matched for age, sex, and initial diagnosis date. Patients with MS had a higher incidence of rheumatoid arthritis (age-adjusted standardized incidence ratio: 1.72; 95% confidence interval = 1.01–2.91). There was a positive correlation in being diagnosed with rheumatoid arthritis in patients previously diagnosed with MS when stratified by sex and age. The strength of this association remained statistically significant after adjusting for sex, age, and smoking history (hazard ratio: 1.78, 95% confidence interval = 1.24–2.56, P = 0.002).In conclusion, this study demonstrates that a diagnosis of MS increased the likelihood of a subsequent diagnosis of rheumatoid arthritis in patients, independent of sex, age, and smoking history.

Anti-SmD and Anti-Sm Antibodies in the Diagnosis of Systemic Lupus Erythematosus

Backgrounds: Anti-Sm antibody is specific to systemic lupus erythematosus (SLE) and is one of the American College of Rheumatologys criteria for SLE. However, the clinical accuracy varies according to different detection systems. This study is to investigate if a new test kit with synthetic anti-SmD3 peptides has a better diagnostic performance. Methods: We used a fluorescent enzyme immunoassay to determine anti-Sm and anti-SmD levels in a SLE group, a rheumatic disease control (rheumatoid arthritis, RA) and a healthy control (HC) group. Receiver operating characteristic curves were constructed and the cut-off value established was able to increase sensitivity of anti-SmD measurement. Results: In total, 213 SLEs, 75 RAs and 108 HCs were studied. Of these, 5.63% of SLEs, 0% of RAs and 0% of HCs were positive for anti-Sm while anti-SmD was positive in 21.13%, 0% and 3.85% of SLE, RA and HC respectively. The sensitivity of anti-Sm and anti-SmD test kit was 5.63% and 21.13% respectively. With the cut-off value analyzed by receiver operating characteristic (ROC) curve, sensitivity was increased to 27.7%. Conclusions: Anti-SmD antibodies have high specificity for SLE and the test kit using SmD3 antigen has better diagnostic performance. In this study population, we identified 27.7% of SLE patients as being was positive for anti-SmD antibodies.