Stress and course of disease in multiple sclerosis

In this prospective study, 96 healthy controls and 101 multiple sclerosis patients were followed up for as many as 6 years, and self-reported stressful events and health status were assessed. The authors evaluated (a) whether patients reported more stressful life events than healthy controls and (b) the bidirectional relationship between stress and functional deterioration among patients. Healthy controls reported more life events than patients, Odds ratio (OR) = 1.13, p < .0001; and this relationship was attributable to healthy controls' reporting more neutral/positive events than patients. A bidirectional relationship was confirmed between stress and illness: there was an increased risk of disease progression when rate of reported stressful events was higher, OR = 1.13, p < .0003, and an increased risk of reported stressful events when rate of disease progression was higher, OR = 2.13, p < .0001. There were no differences in reported stress by level of baseline disability. The authors concluded that multiple sclerosis patients demonstrate a vicious cycle between stress and disease progression.     

Stressful life events precede exacerbations of multiple sclerosis

OBJECTIVE: We longitudinally monitored life events and health changes in patients with multiple sclerosis (MS) to determine whether stressful events may trigger exacerbation of MS. METHODS: Twenty-three women with MS were followed for 1 year. Each subject completed the Psychiatric Epidemiologic Research Interview on a weekly basis. Further information on potentially stressful events was acquired using the Life Events and Difficulties Schedule. Neurologic symptoms were also monitored on a weekly basis throughout the year. Potential MS exacerbations were confirmed by a neurologist who was blind to the presence and timing of stressors. RESULTS: Eighty-five percent of MS exacerbations were associated with stressful life events in the preceding 6 weeks. Stressful life events occurred an average of 14 days before MS exacerbations, compared with 33 days before a randomly selected control date (p < .0001). Survival analysis confirmed that an increase in frequency of life events was associated with greater likelihood of MS exacerbations (hazard ratio = 13.18, p < .05). CONCLUSIONS: These results are consistent with the hypothesis that stress is a potential trigger of disease activity in patients with relapsing-remitting MS.     

Stressful life events, depression and demoralization as risk factors for acute coronary heart disease

BACKGROUND: While the effect of psychological stress and depression on the course of heart disease is commonly recognized, the relationship between recent life events, major depression, depressive symptomatology and the onset of acute coronary heart disease (CHD) has been less considered. The aim of this study was to investigate the presence of stressful life events, major and minor depression, recurrent depression and demoralization in the year preceding the occurrence of a first acute myocardial infarction (AMI) and/or a first episode of instable angina and to compare stressful life events, also related with mood disorders, in patients and healthy controls. METHODS: 97 consecutive patients with a first episode of CHD (91 with AMI and 6 with instable angina) and 97 healthy subjects matched for sociodemographic variables were included. All patients were interviewed with Paykel's Interview for Recent Life Events, a semistructured interview for determining the psychiatric diagnosis of mood disorders (DSM-IV), a semistructured interview for demoralization (DCPR). Patients were assessed while on remission from the acute phase. The time period considered was the year preceding the first episode of CHD and the year before the interview for controls. RESULTS: Patients with acute CHD reported significantly more life events than control subjects (p < 0.001). All categories of events (except entrance events) were significantly more frequent. 30% of patients were identified as suffering from a major depressive disorder; 9% of patients were suffering from minor depression, 20% from demoralization. Even though there was an overlap between major depression and demoralization (12%), 17% of patients with major depression were not classified as demoralized and 7% of patients with demoralization did not satisfy the criteria for major depression. Independently of mood disorders, patients had a higher (p < 0.001) mean number of life events than controls. With regard to life events, the same significant difference (p < 0.001) compared to controls applied to patients with and without mood disorders. CONCLUSIONS: Our findings emphasize, by means of reliable methodology, the relationship between life events and AMI. These data, together with those regarding traditional cardiac risk factors, may have clinical and prognostic implications to be verified in longitudinal studies.     

Macrophage migration inhibitory factor gene: influence on rheumatoid arthritis susceptibility

The macrophage inhibitory factor (MIF) is a cytokine that has been implicated in several inflammatory and autoimmune diseases, including rheumatoid arthritis, systemic lupus, glomerulonephritis, and multiple sclerosis. In rheumatoid arthritis (RA), results ranging from lack of association of MIF polymorphisms with RA, to involvement in either severity or susceptibility to the disease have been reported in the past. We aimed at investigating the role of this gene in RA in the Spanish population. Two well-known MIF promoter polymorphisms were tested in 606 adult RA patients and 886 healthy controls: a single nucleotide polymorphism at -173G/C and a tetranucleotide repeat (CATT)(5-8) located at -794. We found a significant association of the allele -173C with RA (p = 0.01; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.06-1.62). The -173C risk allele, previously reported to be transmitted in excess in patients with juvenile idiopathic arthritis, was significantly more frequent in early-onset adult RA patients than in healthy controls (p = 0.003; OR = 1.57; 95% CI = 1.14-2.15), whereas late-onset patients were not significantly different to controls (p = 0.6; OR = 1.09; 95% CI = 0.77-1.55). In conclusion, the -173C allele in the MIF promoter region is associated with increased RA predisposition, mainly in early-onset patients.     

HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus

Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR?=?3.36; 95% CI?=?1.46–7.74; p?=?.005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR?=?6.47, 95% CI?=?2.58–16.26; p?<?.0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR?=?7.06, 95% CI?=?0.07–2.19; p?=?.002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38?±?28.49?μmol/L) compared to SLE patients HLA-C1 negative (108.37?±?86.09?μmol/L) (p?=?.03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients.     

Predicting Injury Risk in Adolescent Football Players: The Importance of Psychological Variables

Explored the relationship of anger/aggression, attention, andstressful life events to injury while addressing the methodologicallimitations of prior studies. An additional objective was todetermine whether the relationship of stressful life eventsto injury is mediated either by anger (directed either inwardor outward) or by impaired attention, either vigilant (broad,external) or focused (narrow, internal). At the beginning ofsummer practice, 120 first-string high school football playerscompleted measures of anger (Framingham Anger Scale), vigilantattention (Symbol Digit Modalities test), focused attention(Pursuit sub test, MacQuarrie Test of Mechanical Ability), andstressful life events (abbreviated form of the Social ReadjustmentRating Scale as modified for use with adolescents by Coddington,1972). Players were then followed through one season to identifythose injured. Logistic regression indicated that high angerdirected outward (p <.05) and low focused attention (p <.01) increased injury risk, while stressful life events andvigilant attention interacted. Injury risk was elevated whenrecent stress was present (p < .05), and increased as vigilancedecreased, suggesting that stressful life events elevate injuryrisk by reducing vigilance.     

No evidence of association of the KLF12 gene with rheumatoid arthritis in Spanish and Dutch cohorts and a meta-analysis of published data

The aim of the present study was to replicate the previously reported association of KLF12 gene polymorphisms with rheumatoid arthritis (RA). Two independent cohorts from Spain (1,360 RA patients and 1,520 controls) and the Netherlands (1,018 RA patients and 1,150 controls) were genotyped for KLF12 rs1887346 and rs9565072 single-nucleotide polymorphisms using a TaqMan 5'-allele discrimination assay. No evidence of association of RA with the minor T allele of rs9565072 (31.82% vs 33.73%; p = 0.14, odds ratios [OR] 0.92 [95% confidence interval (CI) 0.82-1.03]) or the minor A allele of rs1887346 polymorphism (21.60% vs 21.77%; p = 0.88, OR 0.99 [95% CI 0.87-1.13]) was observed in Spanish patients compared with healthy controls. This lack of association was also confirmed in the Dutch cohort: the minor T allele frequency of rs9565072 in Dutch RA patients was 35.34% versus 35.57% in controls; p = 0.87, OR 0.99 (95% CI 0.87-1.12); and the minor A allele frequency of rs1887346 in Dutch RA patients was 27.64% versus 28.17% in controls; p = 0.70, OR 0.97 (95% CI 0.85-1.12). A meta-analysis of published KLF12 gene association with RA revealed a pooled OR of 0.99 (95% CI 0.93-1.04) for rs1887346 and a pooled OR of 0.99 (95% CI 0.95-1.04) for rs9565072. In conclusion, our findings indicate that the KLF12 rs1887346 and rs9565072 polymorphisms do not play a relevant role in RA.     

Members 6B and 14 of the TNF receptor superfamily in multiple sclerosis predisposition

TNFRSF6B and TNFRSF14 genes were recently associated with Crohn's disease and rheumatoid arthritis. TNFRSF14 is known as herpes virus entry mediator (HVEM), and herpes viruses have been involved in the aetiology of multiple sclerosis (MS). MS patients present human herpes virus 6 (HHV6) in active plaques and increased antibody responses to HHV6. We aimed to ascertain the role of these genes in MS susceptibility and to investigate the relationship of the gene encoding the widely expressed HVEM receptor with the active replication of HHV6 found in some MS patients. Genotyping of 1370 Spanish MS patients and 1715 ethnically matched controls was performed. HHV6A DNA levels (surrogate of active viral replication) were analysed in serum of MS patients during a 2-year follow-up. Both polymorphisms were associated with MS predisposition, with stronger effect in patients with HHV6 active replication-TNFRSF6B-rs4809330(*)A: P=0.028, OR=1.13; TNFRSF14-rs6684865(*)A: overall P=0.0008, OR=1.2; and HHV6-positive patients vs controls: P=0.017, OR=1.69.     

MHC class I chain-related gene A transmembrane polymorphism modulates the extension of ulcerative colitis

Recent evidence from several studies has suggested a genetic predisposition in the pathogenesis of ulcerative colitis (UC), which is especially related with major histocompatibility complex (MHC) genes. The aim of this study was to investigate the possible association of human leukocyte antigen (HLA-B, HLA-DR) and MHC class I chain-related-transmembrane (MICA-TM) polymorphism with the behavior and extension of UC. We selected 121 unrelated patients with UC. These were divided into two groups according to the extension of the disease: 31 patients with distal UC and 90 with wide extension UC; 116 blood donors were also selected as healthy controls, all of whom were typed for HLA-B, HLA-DR, and MICA-TM alleles. HLA-B7 was found to be overrepresented in distal UC patients compared with those with extensive UC (p(c) = 0.007, OR = 5.33) and healthy controls (p(c) = 0.03, OR = 4.09). The MICA-A5.1 allele was also increased in distal UC (p(c) = 0.015, OR = 3.82) when compared with extensive forms. These alleles are in strong linkage disequilibrium in our population. The MICA-A5 allele was significantly increased in extensive forms when compared with healthy controls(p(c) = 0.02, OR = 2.4). According to our results, MICA-A5.1 allele seems to be protective against extensive forms of UC, and MICA-A5 may condition a worse progression of the disease. These results are in agreement with other studies that suggest a similar role of such alleles in other diseases, such as insulin-dependent diabetes mellitus and celiac disease.     

Moderating effects of coping on the relationship between stress and the development of new brain lesions in multiple sclerosis

OBJECTIVE: Many patients with multiple sclerosis (MS) report that stress can trigger disease exacerbations. Considerable research has supported a relationship between stress and both clinical exacerbation and the development of new brain lesions. However, these relationships are not always consistent either within patients or across patients, suggesting the presence of moderators. This study examined the hypothesis that coping moderates the subsequent relationship between stress and the development of new brain lesions in MS. METHODS: Thirty-six patients (mean age = 44.4; 22 women, 14 men) with relapsing forms of MS were assessed once every 4 weeks for 28-100 weeks. New brain lesions were identified using monthly Gd+ MRI. Stress was measured within 24 hours before MRI using a modified version of the Social Readjustment Rating Scale that assessed Conflict and Disruption in Routine. Coping was measured at baseline using the Coping with Health Injuries and Problems questionnaire, which produces four scales: distraction, instrumental, palliative, and emotional preoccupation. Data were analyzed using mixed effects logistic regression to account for within-subject correlations. Analyses were lagged such that stress assessments predicted new Gd+ MRI brain lesions 8 weeks later. RESULTS: As reported previously, stress was significantly related to the development of new Gd+ brain lesions 8 weeks later (OR = 1.62, p =.009). Greater use of distraction was found to be a significant moderator of the relationship between stress and new Gd+ lesions (OR = 0.69, p =.037) such that greater use of distraction was associated with a decreased relationship between stress and new Gd+ lesions. Increased instrumental coping was marginally associated with a decreased relationship between stress and new Gd+ lesions (OR = 0.77, p =.081), while increased emotional preoccupation was marginally associated with an increased relationship between stress and new Gd+ lesions (OR = 1.46, p =.088). There was no significant moderating effect for palliative coping (p =.27) and no significant main effects for any coping variables and the subsequent development of new Gd+ brain lesions (p values >.21). CONCLUSIONS: These findings provide modest support for the hypothesis that coping can moderate the relationship between stress and the MS disease activity. Several limitations in this study are discussed. While these findings suggest areas of potentially fruitful research, readers are cautioned that these are preliminary results; inferences regarding the clinical importance of these findings are premature.     

Determinants of participation in cancer support groups: The role of health beliefs

Background: Although considerable attention has been directed toward cancer support groups, little is known about how often these services are actually used in clinical practice or the factors that influence participation. Purpose: Drawing in part on the Health Belief Model, this study examined group participation and its correlates among 425 patients with diverse malignancies treated at a large academic oncology center. Method: Patients were surveyed regarding utilization rates, health beliefs, and medical and demographic characteristics. Results: Only a small number of patients reported having participated in groups (8.0%). Consistent with the model, in univariate analyses, participation was significantly related to greater perceptions of illness severity (p < .0001), greater perceived benefits (p < .01), fewer perceived barriers (all p < .01), and greater cues for action (i.e., recommendation by family/friends, p < .000001). In multivariate analyses controlling for disease site and other covariates, the strongest predictors included recommendation by family/friends (OR = 5.04; CI = 1.98–12.81), perceived seriousness of the illness (OR = 4.07; CI = 1.42–11.60), and geographical residence (OR = 2.74; CI = 1.09–6.93). Conclusion: Results suggest that participation might be increased by involving the patient’s support network, improving access in underserved rural communities, addressing illness appraisals, and increasing outreach to certain diagnostic groups.     

甲亢患者病前应激性生活事件研究

目的：探讨甲亢患者病前经历的应激性生活事件的特点及与疾病的联系。方法：采用事件量表（ＬＥＳ）对８２例初发的甲亢患者进行测定,并与正常对照比较。结果：甲亢患者病前经历有影响的负性生活事件频数及总生活事件频数、负性生活紧张值及总生活事件紧张值显著高于对照组（Ｐ〈０．０５）,男性患者正性生活事件紧张值显著高于女性患者。结论：提示患病前经历较多负性生活事件的应激可能与发病有一定联系。     

Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations

Coronary artery disease (CAD) has become a major health problem in many countries. Recent genome-wide association studies have identified the association between rs1333049 on chromosome 9p21 and susceptibility to CAD in Caucasoid populations. In this study, we evaluated the associations of rs1333049 with CAD in Japanese (604 patients and 1,151 controls) and Koreans (679 patients and 706 controls). We found a significant association in both Japanese [odds ratio (OR) = 1.30, 95% confidence interval (CI); 1.13–1.49, p = 0.00027, allele count model] and Koreans (OR = 1.19, 95% CI; 1.02–1.38, p = 0.025, allele count model). These observations demonstrated that chromosome 9p21 was the susceptibility locus for CAD also in East Asians.     

HLA class I polymorphisms in Tunisian patients with otosclerosis

Background: Otosclerosis is a common form of hearing impairment among Western-Eurasian adults. The cause of otosclerosis remains unknown. Autoimmune reaction against the otic capsule has been suggested as a possible aetiologic factor in otosclerosis.

Aim: The present study is the first report to evaluate the relationship between class I major histocompatibility complex (MHC) genes (HLA-A, HLA-B and HLA-Cw) and genetic susceptibility to otosclerosis in Tunisian patients.

Subjects and methods: Fifty unrelated Tunisian patients exhibiting clinical otosclerosis were typed for HLA-A, HLA-B and HLA-Cw antigens and compared with 100 ethnically-matched healthy controls.

Results: Increased frequencies of HLA-A*03 (OR = 4.16, Pc < 0.043), HLA-B*35 (OR = 2.76, Pc < 0.043) and HLA-Cw*03 (OR = 4.57, Pc < 0.043) antigens were found in the patients with otosclerosis compared with healthy controls. Individuals with HLA-A*30 (OR = 0.25, Pc < 0.043), HLA-B*51 (OR = 0.11, Pc < 0.043), HLA-Cw*16 (OR = 0.08, Pc < 0.043) and Cw*06 (OR = 0.32, Pc < 0.043) antigens have a protective effect against otosclerosis.

Conclusions: In conclusion, the data suggest that a variation in class I HLA antigens could be a genetic factor involved in susceptibility to otosclerosis in the Tunisian population.     

应激性生活事件对室性心律失常患者血液流变性的影响

目的 :探讨应激性生活事件对室性心律失常患者血液流变性的影响。方法 :采用应激性生活事件量表对 2 0例功能性室性心律失常患者和 2 0例与之在人口统计学方面相匹配的健康人进行了评定并测定血液流变学指标。结果 :病例组高切变率血液粘度 [ηb(H) ]、血浆粘度 ( ηP)、红细胞压积 (HCT)和红细胞聚集性 (AI)与对照组相比差异有非常显著性意义 (P <0 .0 1) ;生活事件紧张总值与上述血液流变学指标呈正性显著相关 (P <0 .0 1)。结论 :应激性生活事件影响血液流变学特性 ,并为应激与室性心律失常关系的研究提供了依据     

Maintenance hormonal treatment improves progression free survival after a first line chemotherapy in patients with metastatic breast cancer

The present study was conducted in patients with metastatic breast cancer. Its aim was to identify the factors which influence progression -free survival (PFS) and overall survival (OS) after the first line of chemotherapy in patients with positive tumour hormone receptor status. The patients with early disease progression during first-line chemotherapy were not included. In total, 560 patients who achieved a stable disease or a response to first-line chemotherapy were studied. The factors identified to improve the duration of PFS or OS in multivariate analysis were: number of metastatic sites (p = .01; p = .01), metastatic sites (p = .02; p = .04), Disease free interval (p = .001; p < .0001), previous hormonal therapy (p = .03; p = ns), response to first line chemotherapy (p < .0001; p = 0.0001) and an administration of maintenance hormonal therapy (p < .0001; p = .001). The major impact obtained by maintenance hormonal treatment after first-line chemotherapy in this study seems to indicate that this strategy should be recommended in patients with an ER or PgR positive tumour.     

Anti-human immunodeficiency virus type 1 antibodies of noninfected subjects are not related to autoantibodies occurring in systemic diseases.

Indeterminate Western blot (WB) (immunoblot) patterns for anti-human immunodeficiency virus type 1 (HIV-1) antibodies are often observed when testing serum samples from noninfected individuals. We investigated here the possible involvement of some frequently occurring autoantibodies (anti-SmB/B', U1snRNP [68 kDa, A, and C], Ro/SS-A [60 and 52 kDa], and Jo-1) in the generation of such indeterminate HIV-1 WB. In particular, the role of a reported sequence homology between p24 gag and the SmB/B' autoantigen was investigated. Serum samples were obtained from 50 healthy controls, 51 patients with systemic lupus erythematosus (SLE), 46 with systemic sclerosis, 6 with Sjögren's disease, 3 with mixed connective tissue disease, and 41 healthy subjects with persistent indeterminate HIV-1 WB. Reactivity to HIV-1 p24 gag was slightly but not significantly more frequent in patients with SLE than in controls (25.5% versus 14.0%; P > 0.1), whereas reactivity to HIV-1 p17 gag was significantly more frequent in the former subjects (23.5% versus 8.0%; P = 0.03). Simultaneous reactivity to p17 and p24 was observed in patients with SLE (11.8%; P = 0.014) or systemic sclerosis (8.7%; P = 0.049) but not in controls. There was no association found between the presence of any autoantibody and the occurrence of indeterminate HIV-1 WB nor between the presence of p24-reactive antibodies and anti-SmB/B'; this indicates that most p24-reactive antibodies are directed to epitopes other than the proline-rich sequences shared by p24 gag and SmB/B'.     

Association of HLA-DR and HLA-DQ genes with susceptibility to pulmonary tuberculosis in Koreans: preliminary evidence of associations with drug resistance, disease severity, and disease recurrence

Only 10% of persons infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB), indicating the existence of host genetic factors regulating disease expression. We investigated the association of human leukocyte antigen (HLA) class II genes with the susceptibility to pulmonary TB in Koreans, with special emphasis on their association with drug resistance, disease severity, and disease recurrence. Human leukocyte antigens (HLA)-DRB1 and -DQB1 gene polymorphisms were analyzed in 160 Korean patients with pulmonary TB and 200 ethnically matched healthy controls. HLA-DRB1*0803 (25.0% vs. 14.5% in controls, OR = 1.97, p = 0.012, corrected p (p(c)) > 0.05) and DQB1*0601 (27.5% vs. 15.5% in controls, OR = 2.07, p = 0.005, p(c) > 0.05) were weakly associated with general susceptibility to TB. DRB1*0803 was significantly associated with drug resistance (30.9% vs. 14.5%, OR = 2.63, p(c) = 0.047) and more advanced lung lesion (29.8% vs. 14.5%, OR = 2.50, p(c) = 0.022). DRB1*0803 showed the strongest association with disease recurrence, especially after curative treatment for the earlier infection (47.4% vs. 14.5%, OR = 5.31, p(c) = 0.00009). DQB1*0601, which is strongly linked to DRB1*0803 in this population showed similar changes in the patients as those of DRB1*0803. It is suggested that DRB1*0803 and DQB1*0601 alleles are associated with disease progression of TB in Koreans, exerting influence on the development of drug resistance, severe disease, and recurrent disease.     

TNF and TNF receptor polymorphisms in Korean Behcet's disease patients

Behcet's disease (BD) is an autoimmune disease characterized by recurrent oral ulcers, genital ulcers, erythema nodosum, and uveitis. Genetic factors are considered important in its pathogenesis. The serum level of tumor necrosis factor (TNF) is elevated in patients with active BD, and its production is elevated in monocytes and in the gamma delta T cells of BD patients. A dramatic response to anti-TNF-alpha antibody treatment further supports the role of TNF in BD. In this study, we investigated genetic polymorphisms of TNF alpha -308 G/A, TNF beta +252 G/A, and TNFR2 196 R/M in 94 Korean BD patients and age- and sex-matched healthy controls to investigate the role of TNF and TNF receptor polymorphisms in BD. The polymerase chain reaction-restriction fragment length polymorphism was used to identify the TNF-alpha promoter (G = TNFA1, A = TNFA2) and TNF-beta intron polymorphisms (G = TNFB1, A = TNFB2), and polymerase chain reaction-singly-strand conformation polymorphism was used to identify TNFR2 196R/M polymorphism (T = TNFR2M, G = TNFR2R). No differences were found in the TNF-alpha, TNF-beta or TNFR2 polymorphisms of the patients and the healthy controls. The allele frequencies of TNFA1/A2 were 0.94/0.06 in patients and 0.96/0.04 in healthy controls (p = 0.36, OR = 0.65, 95% CI = 0.26-1.63), for TNFB1/TNFB2 these were 0.42/0.58 in patients and 0.44/0.56 in controls (p = 0.68, OR = 0.91, 95% CI = 0.61-1.38), and for TNFR2R/TNFR2M 0.23/0.77 in patients and 0.21/0.79 in controls (p = 0.62, OR = 1.13, 95% CI = 0.69-1.84). In conclusion, this study found no differences of TNF alpha -308 G/A, TNF beta +252 G/A or of the TNFR2 196R/M polymorphisms in Korean BD patients versus healthy controls. These findings suggest that the role of TNF in BD is not genetically determined, but can be functionally explained.