title: Tumor necrosis factor alpha promoter polymorphism associated with increased susceptibility to secondary hemophagocytic lymphohistiocytosis in the Korean population.
abstract: 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-alpha). As not all the patients with infection or lymphoma have secondary HLH, we investigated the relationship between susceptibility to secondary HLH and TNF-alpha promoter polymorphisms to identify genetic factors of secondary HLH. We determined the alleles of four promoter sites (-1031/-857/-308/-238) of TNF-alpha 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-alpha -1031C allele, which is associated with higher-plasma TNF-alpha 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-alpha polymorphisms, the haplotype H6 (CTGG) was detected only in the patient group, and the haplotype group (H2 or H5 or H6) including TNF-alpha -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-alpha -1031C allele and its associated haplotypes in Koreans may enhance susceptibility to secondary HLH.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Yoon Hwan
authors.initials: YH
authors.lastname: Chang
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
authors.forename: Heui Seung
authors.initials: HS
authors.lastname: Jo
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Cho
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Sue
authors.initials: S
authors.lastname: Shin
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Ho Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Hong
authors.forename: Seok Il
authors.initials: SI
authors.lastname: Hong
authors.forename: Han Ik
authors.initials: HI
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007723:Korea; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha