BACKGROUND: The tumor necrosis factor (TNF) is believed to play an important role in the pathophysiology of osteoarthritis (OA). Evidence shows that genetic polymorphisms make substantial contributions to the etiology of OA. METHODS: We investigated the genotypes TNF-alpha and TNF-beta in 301 OA patients and 291 healthy subjects as controls. We employed a polymerase chain reaction-restriction fragment length polymorphism and a polymerase chain reaction-single strand conformation polymorphism assay to identify the genotypes TNFA -G308A and TNFB +G252A, respectively. RESULTS: For TNFA -G308A, the percentages of genotypes GG, AG, and AA were 26.3% (79/301), 62.5% (188/301), and 11.3% (34/301) in OA patients and 88.7% (258/291), 11.3% (33/291), and 0% (0/291) in controls. For TNFB +G252A, the percentages of genotypes GG, AG, and AA were 15.3% (46/301), 41.9% (126/301), and 42.9% (129/301) in OA patients and 12% (35/291), 52.6% (153/291), and 35.4% (103/291) in controls. There were significant differences in genotypes and alleles of TNFA -308 between OA patients and controls (p<0.0001) and in alleles of TNFB +252 (p=0.0325). The risk of OA was significantly higher for carriers of the TNFA -308A allele and the TNFB +252 AA homozygote (p=0.0224). CONCLUSIONS: The results suggest close relationships between TNFA -G308A and TNFB +G252A polymorphisms and individual susceptibility to OA in the Korean population.
Alleles ; Genetic Predisposition to Disease ; Genotype ; Homozygote ; Humans ; Lymphotoxin-alpha ; Osteoarthritis ; Polymorphism, Genetic ; Tumor Necrosis Factor-alpha

BACKGROUND AND PURPOSE: Migraine patients are particularly prone to the complication of medication-overuse headache (MOH). Although it has been shown that A allele carriers for the tumor necrosis factor (TNF)-beta gene G252A polymorphism are at high risk of the development of migraine without aura, the relationship between the TNF-beta gene G252A polymorphism and MOH is unknown. We investigated whether the TNF-beta gene G252A polymorphism is involved in the aggravation of migraine by overuse of medications. METHODS: Forty-seven migraine patients (6 males and 41 females; age 36.4+/-10.3 years, mean+/-SD) and 22 MOH patients (1 male and 21 females; age 39.6+/-9.9 years) who had migraine were included in this study. The genotype for the TNF-beta gene G252A polymorphism was determined by polymerase-chain-reaction restriction-fragment-length polymorphism analysis. RESULTS: The distribution of TNF-beta gene G252A genotype frequency differed significantly between migraine and MOH patients (p=0.013). The G/G genotype was carried by 23% of the migraine patients but it was absent in MOH patients. CONCLUSIONS: G/G genotype carriers appear to be less susceptible to the aggravation of migraine by overuse of medications. The G252A TNF-beta gene polymorphism may be one of the factors contributing to the complications of MOH in patients with migraine.
Alleles ; Genotype ; Headache ; Humans ; Lymphotoxin-alpha ; Male ; Migraine Disorders ; Migraine without Aura ; Tumor Necrosis Factor-alpha

OBJECTIVES: Proinflammatory process has been implicated as an underlying mechanism of bipolar disorder and schizophrenia. Previous studies have suggested a possible role of lymphotoxin alpha (LTA) gene in the development of schizophrenia and have prompted further investigation in bipolar patients. Association of the LTA +252A/G polymorphism with susceptibility to bipolar I disorder itself as well as with vulnerability among a subset of psychotic bipolar patients were tested. METHODS: DNA extraction was done by a standard method and genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 114 Korean patients with bipolar I disorder and 202 healthy controls. SPSS v18.0 was used for statistical analysis. Comparisons of the genotype and allele distributions in LTA +252A/G polymorphism were made using a chi-square test. The genotype and allele associations were also evaluated using odds ratio (OR) and 95% confidence interval (CI). Statistical significance was accepted when p was < 0.05. RESULTS: No significant association was found between the LTA +252A/G polymorphism and bipolar disorder. However, LTA +252G allele was present with significantly higher frequency among bipolar patients with psychotic features compared to those without (chi2 = 4.69, p = 0.034, OR = 2.495, 95% CI = 1.069-5.827). CONCLUSION: The results suggest that the allele LTA +252G of the polymorphism may be associated with the psychotic subset of bipolar disorder but not with bipolar I disorder itself. Adequately powered subsequent studies should be conducted.
Alleles ; Bipolar Disorder ; DNA ; Genotype ; Humans ; Lymphotoxin-alpha ; Odds Ratio ; Schizophrenia

OBJECTIVE: To investigate the effects of co-expression of sodium iodide symporter (NIS) reporter gene on the proliferation and cytotoxic activity of chimeric antigen receptor (CAR)-T cells in vitro. METHODS: T cells expressing CD19 CAR (CAR-T cells), NIS reporter gene (NIS-T cells), and both (NIS-CAR-T cells) were prepared by lentiviral infection. The transfection rates of NIS and CAR were determined by flow cytometry, and the cell proliferation rate was assessed using CCK-8 assay at 24, 48 and 72 h of routine cell culture. The T cells were co-cultured with Nalm6 tumor cells at the effector-target ratios of 1∶2, 1∶1, 2∶1 and 4∶1 for 24, 48 and 72 h, and the cytotoxicity of CAR-T cells to the tumor cells was evaluated using lactate dehydrogenase (LDH) assay. ELISA was used to detect the release of IFN-γ and TNF-β in the co-culture supernatant, and the function of NIS was detected with iodine uptake test. RESULTS: The CAR transfection rate was 91.91% in CAR-T cells and 99.41% in NIS-CAR-T cells; the NIS transfection rate was 47.83% in NIS-T cells and 50.24% in NIS- CAR-T cells. No significant difference in the proliferation rate was observed between CAR-T and NIS-CAR-T cells cultured for 24, 48 or 72 h (P> 0.05). In the co-cultures with different effector-target ratios, the tumor cell killing rate was significantly higher in CAR-T group than in NIS-CAR-T group at 24 h (P < 0.05), but no significant difference was observed between the two groups at 48 h or 72 h (P>0.05). Higher IFN-γ and TNF-β release levels were detected in both CAR-T and NIS-CAR-T groups than in the control group (P < 0.05). NIS-T cells and NIS-CAR-T cells showed similar capacity of specific iodine uptake (P>0.05), which was significantly higher than that in the control T cells (P < 0.05). CONCLUSION The co-expression of the NIS reporter gene does not affect CAR expression, proliferation or tumor cell-killing ability of CAR-T cells.
Antineoplastic Agents ; Cell Line, Tumor ; Cell Proliferation ; Iodine ; Lymphotoxin-alpha ; Receptors, Chimeric Antigen ; Symporters ; T-Lymphocytes

OBJECTIVE: To evaluate the levels of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) before and after conservative laparoscopic surgery in patients with endometriosis. METHODS: The levels of TNF-alpha and TNF-beta in the serum of both 82 patients with EMS and 68 controls were determined by ELISA. RESULTS: The levels of TNF-alpha and TNF-beta in the serum of patients with EMS were significantly higher than those of the controls (P < 0.01), and they increased with the clinical terms ( P < 0.05). After clearance of endometrosis foci with laparoscopic conservative surgery, the TNF-alpha levels decreased significantly in EMS III - IV, and TNF-beta levels decreased significantly in EMS I - IV. CONCLUSION Measuring TNF-alpha and TNF-beta levels in the serum of patients with EMS may have important value in postoperative follow-up, surveillance and evaluation of the effectiveness of the surgery.
Adolescent ; Adult ; Endometriosis ; blood ; surgery ; Female ; Follow-Up Studies ; Humans ; Laparoscopy ; Lymphotoxin-alpha ; blood ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVE: To determine the polymorphism in +252 site of tumor necrosis factor-beta(TNF-beta) gene in patients with or without endometriosis, to evaluate the levels of TNF-alpha and TNF-beta in the serum with or without endometriosis, to explore the relation between polymorphism of TNF-beta gene and the genetic susceptibility of endometriosis, and to explore the pathogenic mechanism of endometriosis at gene level. METHODS: By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, polymorphism on +252 site of TNF-beta gene was measured in 82 patients with endometriosis (the endometriosis group) and 80 patients without endometriosis (the control group). With the sandwich-enzyme-linked immunosorbent assay (ELISA), the levels of TNF-alpha and TNF-beta in the serum of the two groups were determined. RESULTS: The TNF-beta level in the serum in the endometriosis group with TNF-beta gene +252 site AA genotype significantly increased, compared with GG genotype (t=2.029, P<0.05); while TNF-alpha and TNF-beta level in the serum had no statistical significance in patients with other genotypes in TNF-beta gene +252 site in the endometriosis group and the control group. CONCLUSION TNF-beta gene +252 site AA genotype might be enhance TNF-beta level in the serum of patients with endometriosis.
Adolescent ; Adult ; Endometriosis ; blood ; genetics ; Female ; Humans ; Lymphotoxin-alpha ; blood ; genetics ; Polymorphism, Genetic ; Tumor Necrosis Factor-alpha ; blood ; Young Adult

The localization and functional characteristics of tumor necrosis factor(TNF) beta gene raise the possibility that it may be involved in the susceptibility to autoimmune thyroid diseases. To investigate whether a TNF beta gene polymorphism is associated with autoimmune thyroiditis, we analyzed the TNF beta gene polymorphism with the restriction enzyme NcoI in 48 Korean patients with atrophic autoimmune thyroiditis [23 were found to be thyrotropin binding inhibitor immunoglobulin(TBII) positive, 25 TBII negative], 52 goitrous autoimmune thyroiditis, and 129 healthy controls. Two TNF beta alleles were identified from the restriction fragment length polymorphism studies of amplified genomic DNA. In atrophic autoimmune thyroiditis patients positive for TBII, 7 of 23 patients were homozygous for the TNF beta * 1 allele, 3 were homozygous for the TNF beta * 2 allele, and 13 were TNF beta * 1/2 heterozygous compared to controls(P = 0.20). Also, there were no associations between the TNF beta gene polymorphism and either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. Of the HLA-class II antigens, the frequency of HLA-DR8 was significantly greater among the 23 Korean patients with TBII-positive atrophic autoimmune thyroiditis compared to control subjects (Pc = 0.003). When the HLA-DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis and controls were analyzed separately, the DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis had more homozygotes for the TNF beta * 1 allele(6/12, 50.0%) and no homozygotes for the TNF beta * 2 allele, as compared to the DR8 negative patients with TBII-positive atrophic autoimmune thyroiditis and DR8 positive controls(P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Alleles ; *Genetic Linkage ; HLA-DR Antigens/*genetics ; Humans ; Korea ; Lymphotoxin-alpha/*genetics ; *Polymorphism, Genetic ; Receptors, Thyrotropin/*immunology ; Thyroiditis, Autoimmune/*genetics

OBJECTIVES: Bipolar disorder is known to have a high genetic predisposition. Recently, the main focus of etiologic studies in bipolar disorder has been concentrated on molecular genetic approach including gene polymorphism analysis. The present study was conducted to investigate whether TNFB polymorphism is associated with bipolar I disorder in the Korean population. METHODS: 89 bipolar I disorder patients diagnosed by DSM-IV criteria were assigned as the patient group and 202 normal population, matched on age and sex from Catholic hemopoietic stem cell bank (Seoul, Korea), were enrolled as the control group in this study. Genotyping was performed by a polymerase chain reaction-restriction fragment length polymorphism method. All data was analyzed by chi2 test. RESULTS: There were no significant differences in frequency of TNFB*1/1, TNFB*1/2 and TNFB*2/2 between bipolar I disorder patient group and normal control group. The frequency of TNFB*2 and TNFB*1 was not statistically different between bipolar I disorder patient group and normal control group. CONCLUSION: The difference of frequency in TNFB*1/TNFB*2 gene between the bipolar I disorder gropup and the normal control could not be verified. The present result suggested that the gene polymorphism of TNFB may not play a significant role in susceptibility to bipolar I disorder. Studies with a larger number of subjects from different ethnic backgrounds, considering clinical phenotype and controlling various factors, should be launched to further determine the role of TNFB in bipolar I disorder.
Bipolar Disorder ; Diagnostic and Statistical Manual of Mental Disorders ; Genetic Predisposition to Disease ; Humans ; Lymphotoxin-alpha* ; Molecular Biology ; Phenotype ; Stem Cells

PURPOSE: Recently, it was reported that tumor necrosis factor (TNF) and lymphotoxin-alpha (LT-alpha) gene regions might be a susceptible loci to type 1 diabetes in Japanese. The purpose of this study was to investigate the association of TNF and LT-alpha gene polymorphisms with disease susceptibility in Korean children with type 1 diabetes. METHODS: Forty-nine Korean children with type 1 diabetes (29 girls and 20 boys) and 94 healthy Koreans were investigated in this study. Genotyping for -857T/C polymorphism in the TNF promoter region and LT-alpha gene polymorphism were performed by PCR-RFLP (restriction fragment length polymorphism). TNF promoter -1031C/T polymorphism was detected by allele-specific PCR. RESULTS: The distribution of the -857T/C and -1031C/T genotype in the TNF promoter region was not different between diabetic children and the controls. The frequency of TT genotype in the distribution of TNF -1031C/T polymorphism in diabetic children with diabetic ketoacidosis (DKA) at diagnosis was significantly lower than those without DKA (P< 0.05). No significant difference in the distribution of LT-alpha gene polymorphism was observed between diabetic children and the controls. There was no association between clinical characteristics of type 1 diabetes and LT-alpha gene polymorphisms. CONCLUSION: These results suggest that TNF promoter -857T/C and LT-alpha gene polymorphisms are not associated with susceptibility to type 1 diabetes in Korean children. TNF promoter -1031C/T polymorphism might be related to clinical manifestations (DKA) of type 1 diabetes.
Asian Continental Ancestry Group ; Child* ; Diabetic Ketoacidosis ; Diagnosis ; Disease Susceptibility ; Female ; Genotype ; Humans ; Lymphotoxin-alpha* ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Tumor Necrosis Factor-alpha*

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Lymphoma ; blood ; diagnosis ; Lymphotoxin-alpha ; blood ; Male ; Middle Aged ; Plasma ; chemistry ; Prognosis ; Tumor Necrosis Factor-alpha ; blood ; Young Adult