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Glucosamine and chondroitin are widely used as pharmaceutical and dietary supplements. However, there is a lack of information regarding consumer consumption of glucosamine and chondroitin in the Republic of Korea. We investigated the prevalence and factors affecting the use of glucosamine products in the general population aged 40 years and older in the Republic of Korea. We conducted this descriptive and exploratory study using a telephone-based survey with a structured questionnaire. We randomly selected subjects using a proportional allocation method based on age, gender, and region. We started the survey on September 19, 2009, and continued the survey until we obtained 1,000 respondents who were currently taking glucosamine or chondroitin, which occured on September 30, 2009. Among the 8,135 people approached, the response rate was 29.6%. A total of 12.2% of respondents ( n = 991) were current users of glucosamine, while only 0.1% ( n = 9) were current users of chondroitin. Two-fifths of current glucosamine users were not diagnosed with osteoarthritis by a doctor nor did they experience arthritis pain. These participants used glucosamine to maintain and promote joint health. Information on glucosamine was mainly obtained through advertisements on television or the Internet. Seventy percent of current users indicated that they did not know the composition of the glucosamine they took. Appropriate information and guides concerning glucosamine or chondroitin usage should be provided by expert clinicians because of the accessibility of both these cartilage derivatives as supplements and medical drugs in the Republic of Korea. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate tumor necrosis factor (TNF) inhibitor persistence and the impact of comorbidity on treatment persistence in patients with rheumatoid arthritis (RA). In a Korean National Health Insurance claims database, patients with a diagnosis code of RA (M05 or M06) who started TNF inhibitor therapy between July 1, 2007 and June 30, 2008 were enrolled. The study cohort was followed until December 31, 2009. Persistence was examined using Kaplan-Meier survival analysis, and multivariate Cox proportional hazard models were developed to examine the potential impact of comorbidities on drug persistence. A total of 388 patients were enrolled in the study cohort. The mean persistence rate in the overall population was 61% at 18 months. Drug survival rates for adalimumab and etanercept at 6 months were 82 and 85%, respectively, and 73 and 78%, respectively, at 12 months. Charlson comorbidity index (CCI) scores and comorbidities such as diabetes, chronic pulmonary disease, mild liver disease, and depression at initiation were not related with drug persistence, while peptic ulcer disease (PUD) lowered the risk of discontinuation of TNF inhibitors (HR 0.73, 95% CI 0.55-0.97). Old age (HR 1.59, 95% CI 1.09-2.33) and prescription of inhibitors by an internist (HR 1.59, 95% CI 1.02-2.48) were associated with discontinuation of TNF inhibitors. The persistence of TNF inhibitors was 61% at 18 months. CCI score and other comorbidities were not related with early discontinuation of TNF inhibitors, while PUD was an independent contributing factor to TNF inhibitor persistence. [ABSTRACT FROM AUTHOR]

The aim of this study is to examine the validity of the rheumatoid arthritis (RA), disease activity score (DAS), 28-C-reactive protein (CRP), the simplified disease activity index (SDAI), and the clinical disease activity index (CDAI) against the DAS28-erythrocyte sedimentation rate (ESR) and determine cut-off values for each tool in Korean patients with RA. A total of 223 RA patients were consecutively recruited from the Hanyang University Hospital for Rheumatic Diseases in Seoul, Korea. DAS28-CRP, SDAI, and CDAI were measured and compared with DAS28-ESR. The correlation coefficients of DAS28-ESR with DAS28-CRP, SDAI, and CDAI were 0.93, 0.85, and 0.84, demonstrating strong linear relationships. The cut-off values of DAS28-CRP classifying RA patients into four categories of disease activity were defined as 2.19, 2.60, and 4.07. SDAI cut-off values were defined as 3.75, 7.50, and 16.88. CDAI cut-off values were defined as 3.62, 7.38, and 16.50. DAS28-CRP, SDAI, and CDAI are valid and sensitive assessment indices of disease activity that are comparable to DAS28-ESR. The cut-off values of each tool derived in this study might be useful for routine monitoring and therapeutic decision-making in Korean RA patients. [ABSTRACT FROM AUTHOR]

Fas and Fas ligand (FasL) polymorphisms in the promoter regions influence transcriptional activities. The interaction of these two genes plays a crucial role in apoptotic cell death regulation. They have been associated with esophageal, lung, uterine cervical, and urinary bladder cancers in human. We performed a case-control study to investigate the association between Fas and FasL polymorphisms and acute myeloid leukemia (AML) risk. Fas−1377G>A (rs2234767), −670T>C (rs1800682), and FasL−844T>C (rs763110) polymorphisms in 592 AML patients and 858 healthy controls were genotyped and tested for associations between polymorphisms and AML risk. There were no significant differences in genotypic and haplotypic distributions and gene-gene interaction between patients and controls in the overall analysis ( p > 0.05). These results suggested that polymorphisms of Fas and FasL genes were not associated with AML risk in the Korean population. [ABSTRACT FROM AUTHOR]

Abstract: N-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects and may be useful for the treatment of inflammatory diseases such as rheumatoid arthritis (RA).We examined the efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on RA on top of standard anti-inflammatory treatment. Patients with RA were randomized into two groups in a double-blind, placebo-controlled, parallel-design multicenter study. One hundred nine patients received five capsules of either n-3 PUFA (2.090 g of EPA and 1.165 g of DHA) or high-oleic-acid sunflower oil for 16 weeks. Eighty-one patients completed the study, and no adverse effects were reported. Dietary intake did not change significantly during the study. There were significant increases in n-3 PUFA and EPA levels in erythrocytes in the n-3 PUFA group versus the placebo group, but decreases in n-6 PUFA, 18:2n6, 20:4n6 and 18:1n9 levels in the n-3 PUFA group versus the placebo group. N-3 PUFA supplementation had no significant effects on nonsteroidal anti-inflammatory drug (NSAID) requirements, clinical symptoms of RA or the concentration of cytokines, eicosanoids and bone turnover markers. However, n-3 PUFA supplementation significantly decreased NSAID requirements and leukotriene B4 levels in patients who weighed more than 55 kg. Our results suggest that n-3 PUFA supplementation has no significant effect on RA but may decrease the requirement for NSAIDs in Korean patients with RA who weigh more than 55 kg. [Copyright &y& Elsevier]

Abstract: Objective: We have noted that quantitative multiplex-methylation specific PCR (QM-MSP) analysis of a key panel of genes may be useful as an ancillary tool for ductal carcinoma in situ (DCIS) detection in breast tissue. In this study, we investigated aberrant promoter hypermethylation of four genes as a means to detect epigenetic alterations specific to breast carcinoma in the serum of patients with DCIS and invasive ductal carcinoma (IDC). Methods: Two hundred forty-three serum samples from 89 patients with IDC, 30 patients with DCIS, and 125 age-matched healthy controls were examined. After DNA extraction and sodium bisulfite treatment, QM-MSP was performed for HIN-1, RASSF1A, RAR-β, and Twist. Results: Overall significant differences in methylation levels were observed for HIN-1 (p =0.006), RAR-β (p <0.001), RASSF1A (p =0.004), and Twist (p <0.001). All four genes showed significantly higher methylation frequencies in DCIS or IDC than in control subjects (p <0.001 for all comparisons). However, methylation frequencies were not significantly different between DCIS and IDC. In receiver-operating characteristic analysis, the two-gene combination (RAR-β/RASSF1A) showed the best performance in distinguishing DCIS/IDC from control samples. The estimated specificity of this two-gene panel for detecting DCIS/IDC was 88.8%, and its sensitivity was 94.1%. Conclusions: The quantitative detection of aberrant DNA methylation in serum samples may be a promising high throughput approach for the diagnosis of breast cancer including DCIS. [Copyright &y& Elsevier]

The Biregional Network of National Control Laboratories (NCLs) of the WHO Western Pacific and South-East Asia Regions has been meeting annually since 2018 to enhance NCLs' voluntary participation capacity. Its seventh meeting was hosted by the Korea National Institute of Food and Drug Safety Evaluation (NIFDS) of the Ministry of Food and Drug Safety (MFDS), in conjunction with the Global Bio Conference, in Seoul on September 6, 2022. Over 60 participants from seven countries, (India, Indonesia, Japan, Korea, Malaysia, the Philippines, and Vietnam) attended the meeting on-site and online. The theme of this meeting was 'Quality Control Issues and International Trends for Biologicals including Vaccines and Plasma-Derived Medicinal Products.' Three special speeches were presented on sharing the quality control system for biologicals, including NCLs' considerations in preparing the WHO Listed Authorities and sharing MFDS experiences. Furthermore, the participating NCLs shared country-specific issues related to national lot releases during the COVID-19 pandemic and acknowledged the meeting's crucial role in response preparedness for pandemic emergencies and enhancing regulatory capacity through coalitions and information exchange among NCLs. The NIFDS will cooperate closely with other Asian NCLs to enhance biological product quality control, aiming to establish regional standards and standardize test methods through collaboration., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To perform a genome-wide association study (GWAS) in Koreans in order to identify susceptibility loci for rheumatoid arthritis (RA)., Methods: We generated high-quality genotypes for 441,398 single-nucleotide polymorphisms (SNPs) in 801 RA cases and 757 controls. We then tested 79 markers from 46 loci for replication in an independent sample of 718 RA cases and 719 controls., Results: Genome-wide significance (P < 5 × 10(-08) ) was attained by markers from the major histocompatibility complex region and from the PADI4 gene. The replication data showed nominal association signals (P < 5 × 10(-02) ) for markers from 11 of the 46 replicated loci, greatly exceeding random expectation. Genes that were most significant in the replication stage and in the combined analysis include the known European RA loci BLK, AFF3, and CCL21. Thus, in addition to the previously associated STAT4 alleles, variants at these three loci may contribute to RA not only among Europeans, but also among Asians. In addition, we observed replication signals near the genes PTPN2, FLI1, ARHGEF3, LCP2, GPR137B, TRHDE, and CGA1. Based on the excess of small P values in the replication stage study, we estimate that more than half of these loci are genuine RA susceptibility genes. Finally, we systematically analyzed the presence of association signals in Koreans at established European RA loci, which showed a significant enrichment of European RA loci among the Korean RA loci., Conclusion: Genetic risk for RA involves both population-specific loci as well as many shared genetic susceptibility loci in comparisons of Asian and European populations., (Copyright © 2011 by the American College of Rheumatology.)

Fas and Fas ligand (FasL) polymorphisms in the promoter regions influence transcriptional activities. The interaction of these two genes plays a crucial role in apoptotic cell death regulation. They have been associated with esophageal, lung, uterine cervical, and urinary bladder cancers in human. We performed a case-control study to investigate the association between Fas and FasL polymorphisms and acute myeloid leukemia (AML) risk. Fas−1377G>A (rs2234767), −670T>C (rs1800682), and FasL−844T>C (rs763110) polymorphisms in 592 AML patients and 858 healthy controls were genotyped and tested for associations between polymorphisms and AML risk. There were no significant differences in genotypic and haplotypic distributions and gene-gene interaction between patients and controls in the overall analysis (p>0.05). These results suggested that polymorphisms of Fas and FasL genes were not associated with AML risk in the Korean population.

Objectives: To analyse the clinical manifestations and severity of Behçet's disease (BD) in Korea according to geographic region of residence, and to identify risk factors associated with clinical severity., Methods: We enrolled 246 BD patients (88 males) who fulfilled the criteria of the International Study Group for BD. These patients were assigned into two groups: a Western group comprising 127 residents in west regions and an Eastern group comprising 119 residents of the SoBaek Mountains situated in the center of Korea. Clinical severity was assessed using a severity scoring index of BD., Results: BD patients from the Western group had a greater prevalence of typical skin lesions, deep vein thrombosis, gastrointestinal bleeding, posterior/ panuveitis, and retinal vasculitis than did the Eastern group (p<0.001, p=0.009, p=0.032, and p=0.007, respectively). The Western group also had higher severity scores than did the Eastern group (5.88±2.5 for the Western group vs. 4.94±2.6 for the Eastern group, p=0.004). Male BD patients had higher severity scores than did female patients (6.14±2.8 vs. 5.03±2.4, p=0.001). The disease duration of BD in the Western group showed a significant association with total severity scores (r=0231, p=0.009), but this was not observed for the Eastern group., Conclusions: We found distinct differences in the clinical manifestations as well as severity of BD according to geographic region in Korean BD patients. Males, particularly those from the Western region of Korea, had significantly higher severity scores than did females.

Introduction: Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) are the most specific serologic marker for rheumatoid arthritis (RA). Genetic polymorphisms in a citrullinating (or deiminating) enzyme, peptidyl arginine deiminase type IV (PADI4) have been reproducibly associated with RA susceptibility in several populations. We investigated whether PADI4 polymorphisms contribute to anti-CCP-negative as well as -positive RA, whether they influence disease severity (erosive joint status), and whether they interact with two major risk factors for RA, Human Leukocyte Antigen-DRB1 (HLA-DRB1) shared epitope (SE) alleles and smoking, depending on anti-CCP and erosive joint status., Methods: All 2,317 unrelated Korean subjects including 1,313 patients with RA and 1,004 unaffected controls were genotyped for three nonsynonymous (padi4&#95;89, padi4&#95;90, and padi4&#95;92) and one synonymous (padi4&#95;104) single-nucleotide polymorphisms (SNPs) in PADI4 and for HLA-DRB1 by direct DNA sequence analysis. Odds ratios (OR) were calculated by multivariate logistic regression. Interaction was evaluated by attributable proportions (AP), with 95% confidence intervals (CI)., Results: A functional haplotype of the three fully correlated nonsynonymous SNPs in PADI4 was significantly associated with susceptibility to not only anti-CCP-positive (adjusted OR 1.73, 95% CI 1.34 to 2.23) but also -negative RA (adjusted OR 1.75, 95% CI 1.15 to 2.68). A strong association with both non-erosive (adjusted OR 1.62, 95% CI 1.29 to 2.05) and erosive RA (adjusted OR 1.62, 95% CI 1.14 to 2.31) was observed for PADI4 haplotype. Gene-gene interactions between the homozygous RA-risk PADI4 haplotype and SE alleles were significant in both anti-CCP-positive (AP 0.45, 95% CI 0.20 to 0.71) and -negative RA (AP 0.61, 95% CI 0.29 to 0.92). Theses interactions were also observed for both non-erosive (AP 0.48, 95% CI 0.25 to 0.72) and erosive RA (AP 0.46, 95% CI 0.14 to 0.78). In contrast, no interaction was observed between smoking and PADI4 polymorphisms., Conclusions: A haplotype of nonsynonymous SNPs in PADI4 contributes to development of RA regardless of anti-CCP or erosive joint status. The homozygous PADI4 haplotype contribution is affected by gene-gene interactions with HLA-DRB1 SE alleles.

We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an association between SLE susceptibility and ITGAM or ITGAM-ITGAX region. The primary objectives of this study are to assess whether single or multiple causal variants from the same gene or any nearby gene(s) are involved in SLE susceptibility and to confirm a robust ITGAM association across nine independent data sets (n = 8211). First, we confirmed our previously reported association of rs1143679 (risk allele 'A') with SLE in EAs (P = 1.0 x 10(-8)) and Hispanic-Americans (P = 2.9 x 10(-5)). Secondly, using a comprehensive imputation-based association test, we found that ITGAM is one of the major non-human leukocyte antigen susceptibility genes for SLE, and the strongest association for EA is the same coding variant rs1143679 (log(10)Bayes factor=20, P = 6.17 x 10(-24)). Thirdly, we determined the robustness of rs1143679 association with SLE across three additional case-control samples, including UK (P = 6.2 x 10(-8)), Colombian (P = 3.6 x 10(-7)), Mexican (P = 0.002), as well as two independent sets of trios from UK (P(TDT) = 1.4 x 10(-5)) and Mexico (P(TDT) = 0.015). A meta-analysis combing all independent data sets greatly reinforces the association (P(meta) = 7.1 x 10(-50), odds ratio = 1.83, 95% confidence interval = 1.69-1.98, n = 10 046). However, this ITGAM association was not observed in the Korean or Japanese samples, in which rs1143679 is monomorphic for the non-risk allele (G). Taken together along with our earlier findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM-SLE association, especially in European- and African-derived populations, but not in Asian populations.

Objective: .In an effort to replicate additional associations of interferon regulatory factor 5 (IRF5) polymorphisms with systemic lupus erythematosus (SLE) in an Asian population, we examined those genetic effects in a Korean SLE cohort., Methods: Each IRF5 polymorphism was genotyped in 1565 subjects using the TaqMan method and examined to determine whether it could explain the association with SLE., Results: Three single-nucleotide polymorphisms (IRF5-15-1, rs2070197, and rs10488631), which showed strong and/or independent association in Caucasian populations, were not polymorphic in our Korean population. Association analysis revealed different genetic effects in Koreans compared with Caucasian populations. In addition, conditional analysis suggested independent genetic effects of 3 variant groups in the Korean population., Conclusion: We demonstrate different genetic effects of IRF5 polymorphisms on the risk of SLE according to ethnicity.

We aimed to evaluate the safety and clinical responses in Korean ankylosing spondylitis (AS) patients after three months of etanercept therapy. AS patients satisfying the Modified New York Criteria were enrolled. They were assessed for safety and clinical responses at enrollment and after three months of etanercept therapy. A total of 124 patients completed the study. After three months, the rate of ASsessment in AS International Working Group 20% improvement (ASAS 20) response was 79.8%. The rates of ASAS 40 and ASAS 5/6 responses were 58.5 and 62.8%, respectively. Significant improvement of Korean version of Bath AS Disease Activity Index (KBASDAI) (p<0.0001), Bath AS Functional Activity Index (BASFI) (p<0.0001), and Bath AS Metrology Index (BASMI) (p=0.0009) were achieved after three months. Quality of life was also significantly improved after three months, as demonstrated by scores for SF-36 (p<0.0001) and EQ-5D (p<0.0001). Erythrocyte sedimentation rate and C-reactive protein were significantly decreased (p<0.0001, p<0.0001, respectively). None of the patients developed tuberculosis and there were no serious adverse event. AS patients with inadequate response to conventional therapy showed significant clinical improvement without serious adverse events after three months of etanercept therapy.

To investigate the diagnostic potential of DNA methylation-based markers in tissue samples of DCIS, we examined the prevalence and extent of methylation in breast ductal carcinoma in situ (DCIS) samples from North American and Korean women. Quantitative multiplex-methylation specific PCR (QM-MSP) of ten genes was performed. The methylation level of APC1, Cyclin D2, HIN-1, RASSF1A and Twist singly, and cumulative methylation of all ten genes was significantly higher in DCIS compared to normal tissues for both groups. A three-gene panel (APC1, HIN-1 and RASSF1A) QM-MSP distinguished between DCIS and normal breast tissues with a sensitivity of 94 to 96% and a specificity of 81 to 87%. Methylation levels of these three genes in DCIS were higher than those of hyperplasia or adjacent normal appearing tissues in Korean women. Comparing North American and Korean DCIS, statistically significant differences in methylation levels were found for CDH1, ERalpha and RAR-beta. Quantification of gene methylation combined with immunohistochemistry in a small subset of tumors suggested that methylation may precede loss of protein expression for ERalpha. Our study demonstrated that methylation profiles of DCIS between North American and Korean women were similar. Methylation status of a panel of genes measured in a quantitative manner accurately discriminated between normal and DCIS tissues of both groups. For both North American and Korean women, QM-MSP analysis of a key panel of genes may be useful as an ancillary tool for DCIS detection in breast tissues.

This study retrospectively investigated the efficacy and adverse events of applying a lower dose (0.5 g/m(2)) of monthly intravenous (IV) cyclophosphamide (CYC) for lupus nephritis in Korean patients. Adverse events occurred in 64 patients (61.5%) of 104 lupus nephritis patients who were treated with IV CYC, with the most common being those related to the gastrointestinal system, followed by infection, symptoms related to the hematopoietic system, skin and its appendages, reproductive system, and urinary system. Lower-dose IV CYC therapy resulted in renal remission or response in 76 patients (73.1%), which was as effective as the reported outcomes of higher-dose (0.75-1.0 g/m(2)) IV CYC regimens. Adverse events were more likely (with borderline statistical significance, p = 0.055) in those who achieved renal remission or response than in nonresponders.

Background: Combined tramadol/acetaminophen is used to treat pain related to osteoarthritis. However, adverse events (AEs) leading to discontinuation can occur. Dose titration may decrease the risk for AEs., Objective: The aim of this study was to assess the effect of tramadol/acetaminophen titration on the development of AEs leading to treatment discontinuation in patients with knee osteoarthritis., Methods: This 2-week, multicenter, randomized, double-blind, double-dummy, add-on study was conducted at 12 tertiary referral university hospitals in the Republic of Korea. Patients aged 35 to 75 years with knee osteoarthritis receiving a stable dose of NSAIDs and with a daily mean pain-intensity score of > or = 4 on a numeric rating scale (NRS) (0 = no pain to 10 = worst pain) during the 48 hours prior to enrollment were eligible. Patients were randomly assigned to receive 1 tablet of tramadol/acetaminophen 37.5/325 mg QD and 1 placebo BID for 3 days, followed by 1 active tablet BID and 1 placebo QD for 4 days, followed by 1 active tablet TID for 7 days (titration group) or 1 tablet of combined tramadol 37.5 mg/acetaminophen 325 mg TID for 14 days (nontitration group). The primary outcome measure was the rate of treatment discontinuation due to AEs. Secondary outcome measures were time to discontinuation due to AEs, prevalences and characteristics of AEs, decrease from baseline in pain intensity as measured on the NRS, and change in the Korean version of the Western Ontario and McMaster Universities (K-WOMAC) index score (scale: 0 = best to 100 = worst)., Results: A total of 250 patients were enrolled (92.0% female; mean [SD] age, 60.2 [7.8] years; mean [SD] weight, 60.0 [9.2] kg [range, 37.5-90.7 kg]; all Korean). The discontinuation rate was significantly lower in the titration group than in the nontitration group (10.5% vs 26.2%; P < 0.001). The Kaplan-Meier survival curve showed that the rates of discontinuation due to AEs were similar in the 2 groups up to day 2, but thereafter the discontinuation rate was significantly lower in the titration group. The most common AEs were nausea (12.1% and 24.6% in the titration and nontitration groups, respectively; P = 0.008), vomiting (4.0% and 17.2%; P < 0.001), and dizziness (9.7% and 22.1%; P = 0.005). No serious AEs were reported in either group. Tramadol/acetaminophen use was associated with a similar decrease from baseline in pain in both the titration and nontitration groups (mean [SD] Delta: NRS, -1.60 [1.62] vs -1.68 [1.58]; total K-WOMAC, -12.86 [13.73] vs -12.52 [16.58])., Conclusions: In this population of Korean patients with knee osteoarthritis pain managed with a stable dose of NSAIDs, titration of tramadol/acetaminophen over 12 days was associated with improved tolerability and a significantly lower discontinuation rate compared with nontitration. Both regimens significantly reduced from baseline associated with osteoarthritis.

Objective: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are rheumatoid arthritis (RA)-specific serologic markers. RA susceptibility has been associated with HLA-DRB1 shared epitope (SE) alleles and single-nucleotide polymorphism (SNP) haplotypes in the peptidyl arginine deiminase 4 gene (PADI4). This study was undertaken to determine whether anti-CCP levels are associated with PADI4 haplotypes and/or SE alleles in Korean patients with RA., Methods: Three nonsynonymous SNPs in PADI4 (padi4&#95;89, padi4&#95;90, and padi4&#95;92) and SE alleles were genotyped, and serum anti-CCP levels were measured, in 311 patients with nonerosive or erosive RA. The relationships between anti-CCP levels and PADI4 haplotypes and/or SE alleles were analyzed statistically., Results: Anti-CCP levels were significantly higher in patients carrying the PADI4 RA risk haplotype than in patients who did not have the risk haplotype, among anti-CCP-positive patients with RA with a disease duration of or=141 months (P = 0.0037) and among those who had erosive RA (P = 0.000098), but not among patients who had a shorter disease duration or those who had nonerosive RA., Conclusion: The PADI4 RA risk haplotype is associated with increased anti-CCP levels in RA patients with disease of short duration, and PADI4 may play a role in early RA. In contrast, SE alleles are associated with increased anti-CCP levels in RA patients with very longstanding disease and in patients with erosive RA, suggesting that SE alleles play a role in very late RA.

Objective: To elucidate the incidence rate and relative risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) and in patients with RA treated with tumor-necrosis-factor (TNF) blockers in Korea., Methods: Using data from the Korean National Tuberculosis Association (KNTA) as a control and data from a single-center cohort of patients with RA, we conducted an evaluation of 1285 patients with RA not exposed to TNF blockers and reviewed medical records of 90 and 103 patients with RA treated with infliximab and etanercept, respectively, between 2001 and 2005., Results: The mean incidence rate of TB, reported by the KNTA, was 67.2 per 100,000 person years (PY) from 2001 to 2004. In the TNF-blocker-naïve RA cohort, 9 cases of TB developed during 3497 PY of followup (257 per 100,000). In the infliximab-treated RA group, 2 cases of TB developed during 78.17 PY of followup (2558 per 100,000 PY), and there was no case of TB during 73.67 PY of followup in the etanercept-treated RA group. The risk of TB was higher in RA patients not treated with TNF blockers (sex- and age-adjusted risk ratio 8.9; 95% confidence interval 4.6-17.2), and in those treated with infliximab (sex- and age-adjusted risk ratio, 30.1; 95% confidence interval, 7.4-122.3) compared with the general Korean population., Conclusion: The risk of TB infection is 8.9-fold higher in Korean patients with RA and 30.1-fold higher in RA patients treated with infliximab, compared with the general Korean population.

Recently, two studies provided convincing evidence that IFN regulatory factor 5 (IRF5) gene polymorphisms are significantly associated with systemic lupus erythematosus (SLE) in several white populations. To replicate the association with SLE in an Asian population, we examined the genetic effects in our SLE cohort from a Korean population. A total of 1,565 subjects, composed of 593 cases and 972 controls, were genotyped using the TaqMan (Applied Biosystems, Foster City, CA, USA) method. The genetic effects of polymorphisms on the risk of SLE were evaluated using chi2 tests and a Mantel-Haenszel meta-analysis. Statistical analysis revealed results in the Korean population were similar to the previous reports from white populations. The rs2004640 T allele had a higher frequency in SLE cases (0.385) than controls (0.321; odds ratio (OR) = 1.32, P = 0.0003). In combined analysis, including all seven independent cohorts from the three studies so far, robust and consistent associations of the rs2004640 T allele with SLE were observed. The estimate of risk was OR = 1.44 (range, 1.34-1.55), with an overall P = 1.85 x 10(-23) for the rs2004640 T allele. The haplotype (rs2004640T-rs2280714T) involved in both the alternative splice donor site and the elevated expression of IRF5 also had a highly significant association with SLE (pooled, P = 2.11 x 10(-16)). Our results indicate that the genetic effect on the risk of SLE mediated by IRF5 variants can be generally accepted in both white and Asian populations.

The incidence of renal cell carcinoma (RCC) in South Korea is steadily becoming similar to that in Western countries. This study summarizes the results of a 3-year multicenter survey of RCC in South Korea, conducted by the Korean Genitourinary Pathology Study Group. A total of 795 cases of RCC were collected from 20 institutes between 1995 and 1997, including 686 clear cell RCCs (86.3%), 58 papillary RCCS (7.30%), 49 chromphobe RCCs (6.16%), and 2 collecting duct RCCs (0.25%). At least 5 years of follow-up was available for 627 clear cell, 54 papillary, and 49 chromophobe RCCs. All subtypes presented most frequently with stage T3aN0M0 at the time of operation, and papillary RCCs demonstrated more frequent lymph node metastasis. Overall survival was not significantly related to the histological subtype (clear cell vs papillary, P = 0.8651; clear cell vs chromophobe, P = 0.0584; papillary vs chromophobe, P = 0.0743). For clear cell RCCs, statistically significant associations were found between overall survival and sex (P = 0.0153), multiplicity (P = 0.0461), necrosis (P = 0.0191), age, sarcomatoid change, TNM stage, nuclear grade, and modality of treatment (all P <0.0001). Overall survival was significantly associated with tumor size (P = 0.0307), nuclear grade (P = 0.0235), multiplicity, sarcomatoid change, and TNM stage (all P <0.0001) for papillary RCCs and with the presence of sarcomatoid change (P = 0.0281), nuclear grade (P = 0.0015), treatment modality (P = 0.0328), and TNM stage (P <0.0001) for chromophobe RCCs. Age (P = 0.0125), nodal stage (P = 0.0010), and treatment modality (P = 0.0001) were significant independent prognostic indicators for clear cell RCC on multivariate analysis. This is the first multicenter study of RCC in South Korea, demonstrating the general patterns and prognostic factors of Korean RCCs.