***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The genes for tumour necrosis factor alpha ( TNF alpha ) and lymphotoxin alpha ( LT alpha ; TNF beta ) are t and emly arranged in the central region of the MHC . They may , therefore , be of importance for the aetiology of MHC-associated diseases . The authors have prospect ively studied the secretion of TNF alpha and LT alpha in relation to polymorphisms at positions -308 and -238 in the TNF alpha gene ( TNFA ) , and two polymorphisms in the first intron of the LT alpha gene ( LTA ) , as well as HLA-DR in 30 patients with chronic inflammatory bowel diseases ( IBD ) and 12 healthy controls . In the Dutch population , the alleles of these four polymorphisms are present in only five combinations , called TNF-haplotypes : TNF-C , -E , -H , -I , and -P. Significant associations between TNF haplotypes and TNF alpha and LT alpha secretion were found when P BMC were cultured with T-cell activators , irrespective of disease . Mean TNF alpha secretion of individuals carrying the HLA-DR3 associated TNF-E haplotype was significantly higher , as compared to individuals without this haplotype ( 26 441 pg/ml versus 19 629 pg/ml ; P = 0.014 ) . Individuals carrying the TNF-C haplotype produced the lowest amount of TNF alpha ( 17 408 pg/ml ; P=0.022 ) . The TNF-C and TNF-E haplotypes differ only at position -308 in the promoter of TNFA . Individuals carrying the HLA-DR1 associated TNF-I haplotype produced significantly less LT alpha when compared to those who lack this haplotype ( 1979 pg/ml versus 3462 pg/ml ; P = 0.006 ) . As the TNF-I haplotype is also associated with low TNF alpha secretion , this haplotype thus defines a ' low secretor phenotype ' . In conclusion , this is the first study to show associations between TNF haplotypes and TNF alpha and LT alpha secretion when T-cell stimulators are used . These findings will contribute to define disease heterogeneity in IBD and may be of relevance for underst and ing the pathogenesis of autoimmune diseases OBJECTIVE To investigate the influence of -308 tumour necrosis factor-alpha ( TNF-alpha ) promoter polymorphism and circulating TNF-alpha levels in the clinical response to the infliximab treatment in patients with rheumatoid arthritis ( RA ) . METHODS One hundred and thirty-two RA patients were genotyped for TNF-alpha promoter by polymerase-chain reaction restriction fragment-length polymorphism ( PCR-RFLP ) analysis . Ten patients with the -308 TNF-alpha gene promoter genotype G/A , and 10 with the G/G genotype were selected and received 3 mg/kg of infliximab at Weeks 0 , 2 , 6 , and 14 . RESULTS Both groups showed a significant improvement with treatment in all variables studied . Total mean TNF-alpha levels increased significantly with respect to basal levels in most of patients after treatment [ probability (p)=0.04 ] . Only patients from G/A showed a statistically significant correlation between ACR 50 and the increase of TNF-alpha levels ( p<0.03 ) . CONCLUSION A relationship was detected between ACR criteria of improvement and increased circulating TNF-alpha levels in RA patients subjected to anti-TNF-alpha therapy OBJECTIVE  Interferon-alpha ( IFNalpha ) has been implicated in the pathogenesis of juvenile dermatomyositis ( DM ) . The aim of this study was to examine serum IFNalpha activity in a cohort of children with juvenile DM to determine relationships between IFNalpha and indicators of disease activity and severity . METHODS Thirty-nine children with definite/probable juvenile DM were included in the study . Serum sample s were obtained at the time of diagnosis from 18 untreated patients with juvenile DM . Second sample s from 11 of these patients were obtained at 24 months , while they were receiving treatment , and third sample s were obtained from 7 of these patients at 36 months . The remaining 21 children were studied 36 months after their initial diagnosis . Serum IFNalpha activity was measured using a functional reporter cell assay . RESULTS Patients with juvenile DM had higher serum IFNalpha activity than both pediatric and adult healthy control subjects . In untreated patients , serum IFNalpha activity was positively correlated with serum muscle enzyme levels ( P<0.05 for creatine kinase , aspartate aminotransferase , and aldolase ) and inversely correlated with the duration of untreated disease ( P=0.017 ) . The tumor necrosis factor alpha -308A allele was associated with higher serum IFNalpha levels only in untreated patients ( P=0.030 ) . At 36 months , serum IFNalpha levels were inversely correlated with muscle enzyme levels in those patients still requiring therapy and with the skin Disease Activity Score in those patients who had completed therapy ( P=0.002 ) . CONCLUSION Serum IFNalpha activity was associated with higher serum levels of muscle-derived enzymes and a shorter duration of untreated disease in patients with newly diagnosed juvenile DM and was inversely correlated with measures of chronic disease activity at 36 months postdiagnosis . These data suggest that IFNalpha could play a role in disease initiation in juvenile DM Objectives To evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-&agr ; polymorphism with regard to the plasma TNF-&agr ; concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit ( SICU ) . Design A total of 112 postoperative critically ill infected patients were prospect ively enrolled . Setting SICU of a tertiary university-affiliated medical center . Patients Patients who were consecutively admitted to the SICU because of surgical infection with sepsis . InterventionBlood sampling . Measurements and Main Results  Blood sample was obtained 24 hrs after intensive care unit ( ICU ) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-&agr ; level and to analyze the genotype of the biallelic polymorphism of the TNF-&agr;. Results The allele frequency of the TNF2 in our infected ICU patients was 12 % . Forty-two ( 37.5 % ) patients admitted fulfilled the criteria of septic shock during their ICU stay . Patients carrying the TNF2 allele were not more likely to develop septic shock , nor did they have a higher mortality rate . In the patients with septic shock , those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype ( 92 % vs. 62 % , p < .05 ) . In those who developed septic shock , the TNF2 allele was significantly associated with higher TNF levels . Conclusion In patients admitted to SICU with surgical infection , the frequency of TNF2 allele was higher than in the general population . SICU patients with TNF2 allele did not show a higher incidence of developing septic shock , nor was there a higher baseline TNF-&agr ; level after infection . However , once septic shock had developed , the mortality rate was higher in those patients carrying the TNF2 allele OBJECTIVE To determine whether the -308 A/G tumor necrosis factor alpha ( TNFalpha ) gene polymorphism can predict the outcome of etanercept therapy in 86 patients with rheumatoid arthritis ( RA ) , as already observed in patients treated with infliximab . METHODS Eighty-six RA patients treated with etanercept  were genotyped for -308 A/G TNFalpha gene polymorphism by polymerase chain reaction and melting curve analysis , using specific gene primers and probes . Patients were subdivided into group A ( G/A genotype ) and group G ( G/G genotype ) . We compared clinical responses to etanercept between groups A and G after 6 months , using the Disease Activity Score in 28 joints ( DAS28 ) . After 12-month treatment , 48 of 86 patients were evaluated again . RESULTS Of 86 patients , 18 ( 21 % ) belonged in group A and 68 ( 79 % ) belonged in group G. After 6-month treatment , 55.6 % of patients in group A and 82.4 % of patients in group G had DAS28 improvement > 1.2 ( P = 0.027 by chi-square ) . The mean + /- SD DAS28 improvement was 1.69 + /- 1.31 in group A and 2.23 + /- 1.19 in group G ( P = 0.098 by t-test ) . After 1-year treatment 48 patients were tested again : 10 ( 21 % ) belonged in group A and 38 ( 79 % ) belonged in group G. Forty percent of patients in group A and 87 % in group G had DAS28 improvement > 1.2 ( P = 0.005 by chi-square ) . The mean + /- SD DAS28 improvement was 1.334 + /- 1.37 in group A and 2.29 + /- 1.47 in group G ( Mann-Whitney U test = 115 , P = 0.0057 ) . CONCLUSION RA patients with a -308 G/G TNFalpha genotype respond to etanercept better than patients with a -308 A/G genotype 
    Output:
    
No association between TNF-α mRNA or protein level expression , and TNF-α -238G/A , -308G/A , -857C/T polymorphisms , studied either independently or in haplotype combinations , was revealed .
Using a meta- analysis for the TNF-α -308 G/A polymorphism , we confirmed the absence of any association between TNF-α mRNA and protein levels , and TNF-α -308 G/A genotypes .
This study and meta- analysis of the literature confirmed the absence of any functional consequences of the TNF-α -308G/A promoter polymorphism , either alone , or in various haplotype combinations in healthy subjects