TNF-α promoter single nucleotide polymorphisms and haplotypes associate with susceptibility of immune thrombocytopenia in Chinese adults.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-α) participates as a candidate susceptibility factor for immune thrombocytopenia (ITP). This study attempted to investigate the association between five single nucleotide polymorphisms (SNPs) spanning the TNF-α promoter and the susceptibility of primary ITP in Chinese Han adults. METHODS: In 215 adult primary ITP patients and 206 healthy controls, SNPs were detected by PCR-RFLP and PCR-SSP. The χ(2) test or fisher's exact test was used to compare frequencies of genotypes and alleles between patients and controls. Haplotypes were analyzed with the SHEsis online program. TNF-α, IFN-γ and Galectin-9 mRNA of 35 newly diagnosed adult ITP patients and 35 healthy controls were detected by qRT-PCR. RESULTS: The haplotype GGC (-238G/-308G/-857C) of TNF-α promoter was significantly associated with a decreased susceptibility of primary ITP, especially in males. The relative levels of mRNA expression of TNF-α, IFN-γ and Gal-9 in adult active primary ITP patients was significantly up-regulated compared with patients in remission and controls. CONCLUSIONS: This study represented the first report that the haplotype GGC of TNF-α was differentially associated with the susceptibility of primary ITP in Chinese Han adults. The up-regulation of TNF-α, IFN-γ and Galectin-9 was significantly correlated with active primary ITP in adult patients.