Tumor necrosis factor alpha promoter polymorphism associated with increased susceptibility to secondary hemophagocytic lymphohistiocytosis in the Korean population

Yoon Hwan Chang, Dongsoon Lee, Heui Seung Jo, Sung Il Cho, Hyung-Jin Yoon, Sue Shin, Jong Hyun Yoon, Ho Young Kim, Young Joon Hong, Seok Il Hong, Han Ik Cho

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Secondary hemophagocytic lymphohistiocytosis (HLH) can be associated with various diseases including infections and lymphoma. The clinical findings of HLH can be explained by an increased production of cytokines such as tumor necrosis factor alpha (TNF-α). As not all the patients with infection or lymphoma have secondary HLH, we investigated the relationship between susceptibility to secondary HLH and TNF-α promoter polymorphisms to identify genetic factors of secondary HLH. We determined the alleles of four promoter sites (-1031/-857/-308/-238) of TNF-α gene by using Taqman®-based allelic discrimination assays in the 66 Korean patients with secondary HLH and 100 healthy Korean controls. We found that the frequency of the TNF-α -1031C allele, which is associated with higher-plasma TNF-α levels, was enriched in patients with secondary HLH compared with healthy controls (OR = 2.00, 95% CI 1.20-3.30, P = 0.007). In haplotype analysis of TNF-α polymorphisms, the haplotype H6 (CTGG) was detected only in the patient group, and the haplotype group (H2 or H5 or H6) including TNF-α -1031C allele was overexpressed in secondary HLH patients (OR = 2.52, 95% CI 1.33-4.77, P = 0.004). These results suggested that TNF-α -1031C allele and its associated haplotypes in Koreans may enhance susceptibility to secondary HLH.

Original languageEnglish
Pages (from-to)45-50
Number of pages6
Issue number1-2
StatePublished - 1 Oct 2006


  • Haplotype
  • Secondary HLH
  • Single-nucleotide polymorphism
  • TNF-α promoter gene

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