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Background While the incidence of paroxysmal noctumalhemoglobinuria (PNH) is relatively high in Northern China,the exact mechanism of the disease remains unknown.Immunoregulatory cytokine polymorphisms can directly regulate the expression levels of cytokines,which play a crucial role in many diseases.The purpose of this study was to study cytokine gene single nucleotide polymorphisms (SNPs) and the correlated cytokine expression levels in relationship to the PNH pathogenesis.Methods Peripheral blood samples were collected from 30 PNH patients and 40 healthy donors; all of the samples were collected from the Han people of Northern China.Eight SNP loci in five cytokine genes,including tumor necrosis factor-alpha (TNF-α),interferon-gamma (IFN-γ),transforming growth factor-beta (TGF-β),interleukin-6 (IL-6),and IL-10,and aplastic anemia (AA) were assessed.TNF-α,TGF-β,IFN-γ,IL-6,and IL-10 were analyzed by sequence-specific primer polymerase chain reaction (PCR-SSP).The plasma protein levels of TNF-α,TGF-β,and IFN-γwere assessed by an ELISA.Results The PNH patients had a lower frequency of the TC/GG genotype of the TGF-I gene (P ＜0.01) and a higher frequency of the C allele in the TGF-β gene (+10) compared to the controls (P ＜0.05).The predominant genotype of the +874 locus of the IFN-γ gene was TA in the PNH patients,while that in the predominant genotype was AA in the control group and was statistically significant (P ＜0.001).The frequency of the T allele in the IFN-γ gene was dramatically higher in the PNH patients than in the controls (P ＜0.05).The PNH patients had a reduced frequency of the GC and CC genotypes,as well as the C allele at locus -174 of the IL-6 gene compared to the controls (P ＜0.01).In addition,the plasma concentrations of TNF-α,TGF-β,and IFN-γ were significantly higher in the PNH group compared to the control group (P ＜0.01). Conclusions Expression levels of the TNF-α,TGF-β,and IFN-γ cytokines play an important role in PNH.The GC and CC genotypes,as well as the C allele of the IL-6 gene may protect the Han people of Northern China against PNH.Additionally,the TC/GG genotype of the TGF-β gene may be the protective allele.In contrast,the TA genotype and the T allele for the IFN-γ gene,as well as the C allele of TGF-β may be susceptible to PNH.However,SNPs in the TNF-α and IL-10 genes did not correlate with PNH development.Alternatively,the increased plasma concentrations of TNF-α,TGF-β,and IFN-γin PNH patients may also be related to PNH development.