The influence of a polymorphism at position -857 of the tumour necrosis factor   gene on clinical response to etanercept therapy in rheumatoid arthritis

Abstract

RA patients with the T allele of TNFA -857C/T SNP respond better to etanercept therapy than homozygotes for the C allele, indicating that, when the results have been confirmed, this SNP could become a useful genetic marker for predicting responses.

TNF-α −308 G/A polymorphism and responsiveness to TNF-α blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis

“…However, there may be a marked decrease in prevalence of the A carrier status among Asians, as only 1.4% of the Korean RA cohort were carriers of this allele. 12 It is of interest that in the Korean RA cohort, patients with the T allele of TNF-a À857 C/T SNP responded better to etancercept therapy than homozygotes of the C allele. 12 This finding has not been replicated in an independent Asian cohort, nor has it been thoroughly investigated in a Caucasian RA cohort.…”

“…12 It is of interest that in the Korean RA cohort, patients with the T allele of TNF-a À857 C/T SNP responded better to etancercept therapy than homozygotes of the C allele. 12 This finding has not been replicated in an independent Asian cohort, nor has it been thoroughly investigated in a Caucasian RA cohort. Therefore, the conclusions of this meta-analysis only pertain to a Caucasian RA population and cannot be generalized to an Asian RA cohort.…”

“…12 Although increased compared with Figure 1, there was no significant heterogeneity (Cochrane Q test P ¼ 0.27; I 2 ¼ 19.6%) among the Caucasian studies ( Figure 2). Again the presence of an A allele was significantly associated with a decreased response to TNF-a inhibitors in RA patients of Caucasian descent ( Figure 2).…”

“…7 At present, there are a handful of small studies that have set out to examine whether the G to A polymorphism at position À308 in the promoter of the TNFa gene influences clinical response to TNF blockade in patients with moderate-to-severe RA. [8][9][10][11][12][13][14][15][16] Owing to the relatively small number of patients exposed to anti-TNF-a agents in all of the pharmacogenetic studies in RA to date, each individual study had insufficient power to conclusively determine if the À308 variant of the TNF-a gene would be helpful in predicting patients that respond poorly to TNF-a blockade. Lee et al 17 carried out a metaanalysis investigating the association of TNF-a À308 G/A polymorphism with responsiveness to TNF-a-blockers in RA.…”

“…The odds of the A allele carrier state was significantly decreased in responders versus nonresponders (OR ¼ 0.41, 95% CI: 0.25-0.68, P ¼ 0.00045; Figure 2). Exclusion of the Korean cohort study 12 did not impact the meta-analysis, as the OR estimated from this study had high variance and only received 1.6% of the total weight in the full meta-analysis. Funnel plots of the ORs from each study against the inverse of their variances were examined with and without the Korean cohort study.…”