肿瘤坏死因子基因多态性与多发性骨髓瘤的临床相关关系

 目的 探讨肿瘤坏死因子α（Tumor necrosis factor alpha，TNFα）基因-308位和淋巴毒素（Lymphotoxin-α，LTα）基因＋252住基因多态性与多发性骨髓瘤（Multiple Myeloma，MM）发病、临床及预后的相关关系。方法 用聚合酶链反应（PCR）、限制性内切酶消化及电泳技术，对32名MM患者和72名正常对照者的TNFα和LTα基N的单碱基突变多态性进行检测，并收集病人组的临床资料，进行生存状况分析。结果 （1）MM病人TNF两位点基因型频率、等住基因频率、联合单倍体分型中各型的频率与对照组比较差异均无统计学意义（P〉0．05）；（2）比较MM病人两位点联合单倍体分型在不同性别、分期、肿瘤负荷、血红蛋白、血钙、血肌酐中的分布，没有发现显著性差异（P〉0．05）；（3）用KaplanMeier方法进行生存分析，没有发现高危型与低危型的总生存时间有显著性差异：在高危型组和低危型组，2年生存率和4年生存率差异无统计学意义（P〉0．05）；Cox回归模型显示两位点联合单倍体分型不是影响预后的危险因素（P〉0．05）。结论 本组研究显示TNFα-308位、LTα＋252住基因多态性在MM病人发病的易感性、临床和预后中可能不起重要作用。

Clinical Relationship between Tumor Necrosis Factor Genetic Polymorphisms and Multiple Myeloma

Objective 　This study was designed to investigate the relationship between-308bp polymorphism in tumor necrosis factor-α( TNFα) gene and + 252bp in lymphotoxin-α(L Tα) gene and the pathogenesis ,clinical course and outcome of multiple myeloma (MM) . Methods 　The single base change polymorphism in TNFα gene and L Tα gene were analyzed among 32 chinese patient s with MM and 72 normal controls by using PCR-rest rictive f ragment length polymorphism ( RFL P) . The clinical data were collected andsurvival analysis was performed. Results 　(1) The difference of dist ribution of genotypes ,alleles of TNFα ( 3/ 308) , L Tα( + 252) and TNF/ L T polymorphic extended haplotypes between the MM patients and control group were not statistically significant ( P > 0. 05) . (2) In patients group , no statistically significant association was found between the presence of a given TNF/ L T haplotype status and clinical characters such as sex , age , clinical stags ,myeloma burthen , hemoglobin , creatinine. (3) The estimated 22year and 42year overall survival rates in the groups of patient s carrying high-risk and low-risk haplotypes were not statistically significant ( P > 0. 05) using Kaplan-Meier method. In multivariate Cox regression models the TNF/L T haplotype status was not found to be risk factors for outcome ( P > 0. 05) . Conclusion 　These data suggest that genetic polymorphisms in the TNFα( 3/308) ,L Tα( + 252) are not crucial in the pathogenesis ,clinical course ,outcome of MM patients.