Chung-Il Joung

Association of guanosine triphosphate cyclohydrolase 1 gene polymorphisms with fibromyalgia syndrome in a Korean population.

Objective. Guanosine triphosphate cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, which is an essential cofactor in nitric oxide (NO) production. Polymorphisms in the GCH1 gene have been implicated in protection against pain sensitivity. The aim of our study was to determine whether single-nucleotide polymorphisms (SNP) in the GCH1 gene affect susceptibility and/or pain sensitivity in fibromyalgia syndrome (FM). Methods. A total of 409 patients with FM and 422 controls were enrolled. The alleles and genotypes at 4 positions [rs3783641(T>A), rs841(C>T), rs752688(C>T), and rs4411417(T>C)] in the GCH1 gene were analyzed. The associations of the GCH1 SNP with susceptibility and clinical measures in patients with FM were assessed. Results. The frequencies of alleles and genotypes of the 4 SNP did not differ between patients with FM and healthy controls. Among 13 constructed haplotypes, we further examined 4 (CCTT, TTCT, TTCA, and CCTA) with > 1% frequency in both FM and controls. No associations of GCH1 polymorphisms with FM-related activity or severity indexes were found, although the number and total score of tender points in patients with FM differed among the 4 haplotypes (p = 0.03 and p = 0.01, respectively). The CCTA haplotype of GCH1 was associated with significantly lower pain sensitivity and occurred less frequently than the CCTT haplotype in patients with FM (p = 0.04, OR 0.45, 95% CI 0.21–0.96). Conclusion. Our study provides evidence that certain GCH1 haplotypes may be protective against susceptibility and pain sensitivity in FM. Our data suggest that NO is responsible for pain sensitivity in the pathogenesis of FM.

Association between the HLA-DRB1 gene and clinical features of systemic sclerosis in Korea

Objective: To determine whether HLA‐DR alleles are associated with the development and clinical features of systemic sclerosis (SSc) in Koreans. Methods: Seventy‐nine patients (74 women and five men; 45 diffuse types and 34 limited types; mean age at diagnosis 43.9 years) fulfilling the American College of Rheumatology (ACR) classification criteria for SSc were enrolled. The controls were 144 healthy, disease‐free Koreans. HLA‐DRB1 genotypes were assessed by the polymerase chain reaction‐sequence specific oligonucleotide probe (PCR‐SSOP) method. Results: The HLA‐DRB1*15 allele was increased in anti‐topoisomerase I autoantibody (anti‐topo I)‐positive SSc patients [p = 0.003, p corrected (pcorr) = 0.039, odds ratio (OR) = 3.43, 95% confidence interval (CI) 1.45–8.13] compared with controls. The DRB1*11 allele was also observed more frequently in anti‐topo I‐positive SSc than in controls (13.3% vs. 4.2%) but not statistically significant (p = 0.053, pcorr = 0.689). In patients with SSc, the DRB1*04 allele was associated with subcutaneous calcinosis (p = 0.048, OR = 4.56, 95% CI 1.07–19.37). Patients with overlap syndrome showed a negative association with the DRB1*04 allele (p = 0.036, OR = 0.26, 95% CI 0.08–0.91). Conclusion: The HLA‐DRB1*15 allele was associated with the development of anti‐topo I‐positive SSc in Koreans. In addition, the DRB1*04 allele was associated with certain clinical features in SSc patients.

Smoking habits influence pain and functional and psychiatric features in fibromyalgia.

OBJECTIVE Numerous epidemiologic data have shown that smoking may play a role in the disease manifestations or severity of chronic musculoskeletal pain. The authors of the present study investigated the effect of smoking on clinical features such as pain, fatigue, functional impairment, and psychiatric features in the Korean population with fibromyalgia syndrome (FMS). METHODS A total of 336 patients with FMS were consecutively enrolled from 10 medical centers which participated in the Korean national fibromyalgia survey. Smoking was divided into current smokers and non-smokers. Instruments of FMS assessment included tender points, Fibromyalgia Impact questionnaire (FIQ), 36-item Medical Outcomes Study Short-Form Health Survey (SF-36), Brief Fatigue Inventory (BFI), Brief Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI)-1 and STAI-2, and social family support and social friend support. Statistical analyses included Chi-square test, Fishers exact test, Mann-Whitney U test, and multivariate logistic regression analysis. RESULTS Thirty-three patients (9.8%) out of 336 participants were current smokers. The number of tender points (P=0.037), BFI (P=0.026), general health of SF-36 (P=0.028), BDI (P=0.014), syncope (P=0.024), and reflex sympathetic dystrophy (P=0.003) showing significance between current smokers and non-smokers were not associated with smoking habits after adjustment. The significance of the number of tender points (P=0.009), scores of total tender points (P=0.032), BDI (P=0.038), general weakness (P=0.047), and reflex sympathetic dystrophy (P=0.011) was observed between randomized non-smokers (n=55) and smokers (n=33). In addition, the number of tender points (P=0.027, OR=1.379) was associated with smoking status after adjustment. The analysis between randomized non-smokers (n=45) and smokers (n=22) in female FMS patients showed that BDI in FMS was associated with smoking status (P=0.023, OR=1.077) after logistic regression analysis. CONCLUSIONS This study revealed that smoking habits may, in part, influence pain or functional and psychiatric features in FMS patients. The impact of smoking on clinical features in FMS should be assessed in a larger study population.

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism in Korean Patients with Systemic Sclerosis

To determine whether angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is associated with the development and clinical features of systemic sclerosis (SSc) in Korean, we studied seventy two Korean patients with SSc fulfilling the ACR preliminary classification criteria. The controls were 114 healthy, disease free Koreans. ACE I/D genotypes were determined by PCR method using oligonucleotides. Sixty eight patients (94.4%) were women and age at diagnosis was 43.5±12.6 yr old (mean±SD). Thirty nine patients (54.2%) had a diffuse type of SSc. There were no statistical differences in the frequencies of all ACE I/D genotypes and D allele between patients and controls, and neither between diffuse and limited types of SSc. ACE I/D gene polymorphism was not associated with the development of SSc in Korea. The investigation for the pathogenesis of SSc requires more studies about the role of other candidate genes such as endothelin, TGF-β, nitric oxide, or angiotensin II receptor in addition to the ACE genes.

Determinants of quality of life in patients with fibromyalgia: A structural equation modeling approach

Objective Health-related quality of life (HRQOL) in patients with fibromyalgia (FM) is lower than in patients with other chronic diseases and the general population. Although various factors affect HRQOL, no study has examined a structural equation model of HRQOL as an outcome variable in FM patients. The present study assessed relationships among physical function, social factors, psychological factors, and HRQOL, and the effects of these variables on HRQOL in a hypothesized model using structural equation modeling (SEM). Methods HRQOL was measured using SF-36, and the Fibromyalgia Impact Questionnaire (FIQ) was used to assess physical dysfunction. Social and psychological statuses were assessed using the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the Arthritis Self-Efficacy Scale (ASES), and the Social Support Scale. SEM analysis was used to test the structural relationships of the model using the AMOS software. Results Of the 336 patients, 301 (89.6%) were women with an average age of 47.9±10.9 years. The SEM results supported the hypothesized structural model (χ2 = 2.336, df = 3, p = 0.506). The final model showed that Physical Component Summary (PCS) was directly related to self-efficacy and inversely related to FIQ, and that Mental Component Summary (MCS) was inversely related to FIQ, BDI, and STAI. Conclusions In our model of FM patients, HRQOL was affected by physical, social, and psychological variables. In these patients, higher levels of physical function and self-efficacy can improve the PCS of HRQOL, while physical function, depression, and anxiety negatively affect the MCS of HRQOL.

Identifying fibromyalgia subgroups using cluster analysis: Relationships with clinical variables

Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns.

Muscular amyloidoma presenting as inguinal masses in multiple myeloma

We report a case with protruding inguinal masses for 6 months, in whom muscular amyloidoma was not suspected before muscle biopsy. On pelvic magnetic resonance imaging (MRI), round masses showing peripheral rim enhancement with gadolinium were observed in iliopsoas and iliacus muscles of both inguinal areas. The same lesions were also observed in gluteus muscles. The biopsy showed Congo red positive materials in a dense fibrous background. Serum and urine electrophoresis showed Bence Jones protein, lambda type. In bone marrow section, myeloma cells were found. Peripheral blood stem cell transplantation (PBSCT) following four cycles of VAD (vincristine, adriamycin, dexamethasone) chemotherapy was performed and the result was satisfactory. Amyloidoma lesions decreased in size and number on the following MRI.

Polymorphisms of the TRPV2 and TRPV3 genes associated with fibromyalgia in a Korean population

OBJECTIVE Researchers continue to gather evidence that transient receptor potential vanilloid (TRPV) channels contribute towards pain signalling pathways. However, it is unknown whether polymorphisms of the TRPV gene are associated with FM. For the first time, we investigated the association between the polymorphisms of the TRPV2 and TRPV3 genes, FM susceptibility and the severity of the symptoms. METHODS A total of 409 patients with FM and 423 controls were enrolled from 10 medical centres that participated in the Korean nationwide FM survey. The alleles and genotypes at three positions [rs3813768(C > G), rs8121(C > T) and rs1129235(C > A)] in the TRPV2 gene and two positions [rs7216486 (G > A) and rs395357(C > T)] in the TRPV3 gene were genotyped. RESULTS The frequencies of the alleles and genotypes of individual TRPV2 and TRPV3 genes were not significantly associated with FM susceptibility. However, the GTA haplotype of TRPV2 showed a defence against FM susceptibility (P = 0.035). In addition, polymorphisms of TRPV3 were associated with symptom severity in FM patients. The single nucleotide polymorphism rs395357 of TRPV3 was associated with the scores of the Brief Fatigue Inventory (P = 0.017) in FM patients. Furthermore, haplotypes of TRPV3 were associated with the Brief Fatigue Inventory and the 36-item Short-Form Health Survey mental health summary scores (P = 0.036). CONCLUSION This study was the first to evaluate the associations of TRPV gene polymorphisms with FM. Our results suggest that certain TRPV2 haplotypes may have a protective role against FM and that some genotypes and haplotypes of TRPV3 contribute towards the symptoms of FM.

Association between catechol‐O‐methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case–control study

Although polymorphisms of the catechol‐O‐methyl transferase (COMT) gene have been implicated in altered pain sensitivity, results concerning the association between COMT gene polymorphisms and fibromyalgia (FM) are equivocal. We assessed the associations between COMT single‐nucleotide polymorphisms (SNP) and FM risk and symptom severity.

Aberrant expression of interleukin-10 and activation-induced cytidine deaminase in B cells from patients with Behçet's disease

Despite extensive studies, the pathogenesis of Behçets disease (BD) remains unclear. In particular, the roles of B cells in patients with BD have not been elucidated. Activation-induced cytidine deaminase (AID) is a critical enzyme for immunoglobulin (Ig) heavy chain class switching and somatic hypermutation in B cells and the abnormal expression of AID in various immune conditions has previously been studied. B10 cells, an interleukin (IL)-10-secreting subset of regulatory B cells, function to downregulate inflammation and autoimmunity. Thus, in the present study, the relevance of B cells in patients with BD was investigated. The plasma levels of IL-10 and IgA and the proportions of cluster of differentiation (CD)43+ B cells, excluding naïve B cells, were measured in 16 patients with BD and 16 age- and sex-matched healthy controls (HCs). Additionally, the mRNA levels of IL-10 and AID were assessed in B cells from fresh peripheral blood samples of the BD patients and HCs. The plasma level of IL-10 in patients with BD did not differ significantly from that in HCs. Similarly, there was no significant difference in the plasma level of IgA, although a slight increase was observed in patients with BD compared with that in HCs. There were no differences in CD43+CD19+ B cell numbers between patients with BD and HCs. However, IL-10 mRNA levels were significantly reduced (P<0.05), while AID mRNA levels were significantly increased (P<0.01) in the B cells of patients with BD compared with those in HCs. These results provide insight into the role of B cells in patients with BD.