中文摘要：

目的探讨肿瘤坏死因子α（TNF-α）编码基因单核苷酸多态性（SNP）位点-308G〉A和-238G〉A基因型与骨髓增生异常综合征（MDS）发生的易感性。方法人组341例原发性MDS患者，对照组为365名与患者无血缘关系的健康志愿者。采用TaqMan探针法对研究人群TNF．cc编码基因SNP位点TNF廿308G〉A、TNF-α-238G〉A进行基因分型。用放射免疫法测定血清TNF-α水平。结果与正常对照组比较，TNF-α-308AA＋AG基因型及A等位基因频率在MDS-难治性血细胞减少伴有多系发育异常（RcMD）患者中增加（18％对10％，P=0．015；9％对5％，P=0．021）。MDS患者TNF-α-308及TNF-α-238G〉A基因型及等位基因频率和正常对照组的比较差异均无统计学意义（P值均〉0．05）。MDS患者TNF-α-308G〉A、TNF-α-238G〉A基因型对血清TNF-α水平无明显影响。TNF-α-308G〉AGG基因型与AA＋AG基因型MDS患者的血小板计数[58（1～611）×10^9／L对90（7～352）×10^9／L]和骨髓原始细胞比例比较差异有统计学意义（P值分别为0．024、0．019）。结论TNF-α-308G〉A基因多态性与MDS．RCMD患者发生的易感性相关。

英文摘要：

Objective To investigate the association of single nucleus polymorphisms （SNP） of tumor necrosis factor alpha （TNF-ct） gene （- 308 G〉A and-238 G〉A genotypes） with susceptibility to primary myelodysplastic syndromes （MDS）. Methods Two SNPs （TNF-α-308 G〉A,TNF-α-238 G〉A） of TNF-α gene were detected by Taqman probes in 341 MDS patients and 365 unrelated-healthy controls. Results Compared to healthy controls, the frequency of TNF-α-308 AA ＋ AG genotype and A allele increased （18% vs 10%, P=-0.015, 9% vs 5%, P=-0.021, respectively） in refractory cytopenia with multilineage dysplasia （RCMD） patients. There was no correlation of TNF-α-308 G〉A genotype and allele frequency between MDS and controls. No difference in the genotype and allele frequency of TNF-α-238 G〉 A were found between controls and MDS or the subtypes of MDS （P〉0.05）.We did not find any linkage between plasma level of TNF-α and TNF-α-308 G〉A or TNF-α-238 G〉A genotype. Statistic differences were observed between platelet count E58（ 1-611 ） ×10^9/L vs 90（7-352） × 10^9/L] and bone marrow blasts in MDS patients carrying TNF-α-308 G〉A GG and AA ＋AG genotype （P=0.024, 0.019, respectively）. Conclusion TNF-α-308 G〉A polymorphism was correlated with susceptibility to MDS-RCMD.