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Family-based analysis of tumor necrosis factor and lymphotoxin-alpha tag polymorphisms with type 1 diabetes in the population of South Croatia.

ABSTRACT: Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) are cytokines with a wide range of inflammatory and immunomodulatory activities. Type 1 diabetes is an autoimmune disease characterized by destruction of insulin-producing pancreatic beta cells. The aim of the present study was to evaluate the association of polymorphisms in the TNF/LTA gene region with susceptibility to type 1 diabetes. We investigated 11 TNF/LTA tag polymorphisms, designed to capture the majority of common variation in the region, in 160 trio families from South Croatia. We observed overtransmission of alleles from parents to affected child at five variants: (rs909253, allele C, p = 1.2x10(-4); rs1041981, allele A, p = 1.1x10(-4); rs1800629 (G-308A), allele A, p = 1.2x10(-4); rs361525 (G-238A), allele G, p = 8.2x10(-3) and rs3093668, allele G, p = 0.014). We also identified overtransmission of the rs1800629(G-308A)-rs361525(G-238A) A-G haplotype, p = 2.384x10(-5). The present study found an association of the TNF/LTA gene region with type 1 diabetes. A careful assessment of TNF/LTA variants adjusted for linkage disequilibrium with HLA loci is needed to further clarify the role of these genes in type 1 diabetes susceptibility in the population of South Croatia.

SUBMITTER: Boraska V

PROVIDER: S-EPMC2709221 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Family-based analysis of tumor necrosis factor and lymphotoxin-alpha tag polymorphisms with type 1 diabetes in the population of South Croatia.

Boraska Vesna V Zeggini Eleftheria E Groves Christopher J CJ Rayner Nigel W NW Skrabić Veselin V Diakite Mahamadou M Rockett Kirk A KA Kwiatkowski Dominic D McCarthy Mark I MI Zemunik Tatijana T

Human immunology 20090122 3

Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) are cytokines with a wide range of inflammatory and immunomodulatory activities. Type 1 diabetes is an autoimmune disease characterized by destruction of insulin-producing pancreatic beta cells. The aim of the present study was to evaluate the association of polymorphisms in the TNF/LTA gene region with susceptibility to type 1 diabetes. We investigated 11 TNF/LTA tag polymorphisms, designed to capture the majority of common variation in th ...[more]

PMID: 19167443

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Project description:AimTo investigate associations between the tumor necrosis factor alpha (TNF-α) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea.MethodsHepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms, which are TNF-α -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-α genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC.ResultsNone of the TNF-α polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-α -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-α -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-α -1031/-238 TT/GA (AOR = 21.576, 95%CI: 2.581-180.394, P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α -1031/-863/-857/-308/-238 T-C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-α -1031/-857/-308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-α -1031/-857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-α -1031/-308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-α -1031/-238 T-A (OR = 10.865, 95%CI: 2.473-47.740, P = 0.0001). Moreover, HCC Okuda stage III cases with the TNF-α -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323).ConclusionAlthough no single TNF-α polymorphism is associated with HCC in this study, some TNF-α genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases with the TNF-α -1031 TT genotype may have a better prognosis than those with the CC genotype.

Dataset Information

Family-based analysis of tumor necrosis factor and lymphotoxin-alpha tag polymorphisms with type 1 diabetes in the population of South Croatia.

Publications

Family-based analysis of tumor necrosis factor and lymphotoxin-alpha tag polymorphisms with type 1 diabetes in the population of South Croatia.

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