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多发性骨髓瘤中的DNA修复基因多态性:与XRCC1(Arg399Gln)多态性无关联,但XRCC4(内含子3中的VNTR和G-1394T)及XPD(Lys751Gln)多态性与土耳其患者的该疾病相关。

DNA repair genes polymorphisms in multiple myeloma: no association with XRCC1 (Arg399Gln) polymorphism, but the XRCC4 (VNTR in intron 3 and G-1394T) and XPD (Lys751Gln) polymorphisms is associated with the disease in Turkish patients.

作者信息

Cifci S, Yilmaz M, Pehlivan M, Sever T, Okan V, Pehlivan S

机构信息

Department of Internal Medicine, School of Medicine, Gaziantep, Turkey.

出版信息

Hematology. 2011 Nov;16(6):361-7. doi: 10.1179/102453311X13127324303399.

DOI:10.1179/102453311X13127324303399
PMID:22183071
Abstract

OBJECTIVE

This study aims to investigate the association between the polymorphisms in DNA repair genes (XPD, XRCC1, and XRCC4) and clinical parameters in patients with multiple myeloma (MM), their effects on prognosis and their roles in susceptibility to MM.

PATIENTS AND METHODS

Sixty patients, diagnosed with MM and 70 individuals as the healthy control group were included in the study. Gene polymorphisms were detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism method. When the genotype frequencies of XPD (Llys751Gln) and XRCC1 (Arg399Gln) genes were examined in the patient and control groups, no significant difference was detected, while a significant association was found in XRCC4 (VNTR in intron 3 and G-1394T) polymorphisms. A significant association was found in the MM patients group for AA genotype and event-free survival (EFS) in terms of XPD (751) gene polymorphism (P = 0.047). When VNTR intron 3 polymorphism was compared for genotype frequency, DD genotype was found to be significantly low (P = 0.012) in the patient group, whereas GG and TT genotypes were found to be significantly lower in the patient group for the genotype frequency XRCC4 (G-1394T) polymorphism when compared to the control group (P = 0.015, P = 0.010, respectively).

RESULTS

These data provide support for the hypothesis that a common variation in the genes encoding XRCC4 DNA repair proteins may contribute to susceptibility to myeloma. These findings require further validation in independent populations.

摘要

目的

本研究旨在探讨DNA修复基因(XPD、XRCC1和XRCC4)多态性与多发性骨髓瘤(MM)患者临床参数之间的关联、它们对预后的影响以及在MM易感性中的作用。

患者与方法

本研究纳入了60例诊断为MM的患者和70例作为健康对照组的个体。采用聚合酶链反应和/或聚合酶链反应-限制性片段长度多态性方法检测基因多态性。在患者组和对照组中检测XPD(Lys751Gln)和XRCC1(Arg399Gln)基因的基因型频率时,未发现显著差异,而在XRCC4(内含子3中的VNTR和G-1394T)多态性中发现了显著关联。就XPD(751)基因多态性而言,MM患者组中AA基因型与无事件生存期(EFS)之间存在显著关联(P = 0.047)。比较VNTR内含子3多态性的基因型频率时,发现患者组中DD基因型显著较低(P = 0.012),而与对照组相比,患者组中XRCC4(G-1394T)多态性的基因型频率中GG和TT基因型显著较低(分别为P = 0.015,P = 0.010)。

结果

这些数据支持了以下假设,即编码XRCC4 DNA修复蛋白的基因中的常见变异可能导致骨髓瘤易感性。这些发现需要在独立人群中进一步验证。

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