多发性骨髓瘤本周蛋白基因可变区特点与肾小管功能损害的关系  

The relation between Bence Jones protein gene polymorphism and function of renal tubular-epithelial cell in multiple myeloma

作　　者：周振海[1] 罗绍凯[1] 李娟[1] 李小银[1] 李幼姬[2] 洪文德[1] 

机构地区：[1]中山大学附属第一医院血液内科,广州510080 [2]中山大学附属第一医院肾内科,广州510080

出　　处：《中华内科杂志》2005年第9期677-680,共4页Chinese Journal of Internal Medicine

摘　　要：目的本周蛋白(BJP)在多发性骨髓瘤(MM)肾损害中起主要作用,本研究试图探讨BJP基因可变区特点与肾小管功能损害的关系。方法将初诊时肾小管功能明显损害且肾组织穿刺活检提示管型肾病的患者分为损害组,确诊后长期BJP阳性而肾小管功能正常的MM患者为无损害组,根据BJP不同,分为BJPκ组与BJPλ组。常规抽取所有患者骨髓提取单个核细胞,提取总RNA,逆转录成cDNA,PCR扩克隆BJP可变区基因、测序,通过Internet网与GenBank已收录的轻链可变区基因序列进行比较及分析。结果损害组可变区的互补决定区(CDRS)R(replacement)突变比例(7·57±3·40)明显高于无损害组(4·25±1·90)及同组骨架区(FWRS)(3·29±1·25),BJPλ组可变区CDRS的R突变比例(6·64±2·38)明显高于BJPκ组(4·10±2·13)及同组FWRS区(2·91±0·94);损害组中λ亚型的同源型以V3-4最多。结论BJPλ型患者的肾损害发生率高可能与其BJP基因可变区R突变比例高,从而导致其BJP结构及理化活性的改变有关;可能某些亚型BJP较易发生肾小管损害。Objective Bence Jones protein （BJP） plays an important role in multiple myeloma （MM） renal lesion, we try to study the relation between the characteristics of BJP variable gene and the function of renal tubular-epithelial cell （TEC）. Methods MM patients whose function of TEC was abnormal at diagnosis constituted a group damage and patients whose function of TEC was normal for a long period a group normal. We also collected MM patients and divided them into a group BJPκ and a group BJPλ. Total RNAs were isolated from the mononuclear cells of bone marrow and reverse transcription was carried out with an oligo dT18 primer; these cDNAs were then amplified with PCR, cloned and sequenced, the comparison and analysis of the sequences were made according to current ESBC/Gen Bank sequence directories. Results 3/5 cases of BJPλ use V3-4 gene in the group damage, the replacement R mutation ratio of CDRS in the group damage（7.57±3. 40） was higher than that in the group normal （4. 25 ± 1.90） and higher than that of FWRS in the group damage（3.29 ± 1.25） ; R mutation ratio of CDRS region in the group BJPh（ 6. 64 ± 2. 38 ）was higher than that in the group BJPκ （4. 10 ± 2. 13 ）and higher than that of FWRS in the group BJPλ（2.91 ±0. 94）, R mutation ratio of CDRS both in the group BJPκ or BJPκ was higher than that of FWRS respectively. Conclusions The higher ratio of renal lesion in some MM patients and BJPλ patients is correlated with the high ratio of their variable gene R mutation which result in changing organization and physicochemical activity of BJP. BJP translated by some subtype genes may incline to injure the function of TEC.

关 键 词：多发性骨髓瘤 本周琼蛋白质 基因 肾小管功能 肾小管功能损害 可变区基因 蛋白基因 Internet网 BJP 单个核细胞 

分 类 号：R733.3[医药卫生—肿瘤]