LRP1B Polymorphisms Are Associated with Multiple Myeloma Risk in a Chinese Han Population
LRP1B Polymorphisms Are Associated with Multiple Myeloma Risk in a Chinese Han Population
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LRP1B 多态性与中国汉族人群的多发性骨髓瘤风险相关
DOI：
10.7150/jca.28905
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发表时间：
2019-01
影响因子：
3.9
通讯作者：
Qin Dongchun
中科院分区：
文献类型：
--
作者：
Li Bingjie;Liu Chenxi;Cheng Guixue;Peng Mengle;Qin Xiaosong;Liu Yong;Li Yongzhe;Qin Dongchun
多发性骨髓瘤（MM）是一种极其复杂的浆细胞恶性肿瘤，具有遗传异质性。最近的一项全基因组关联研究（GWAS）表明，2q22 （rs61070260）的变异会影响MM的风险。到目前为止，这种关联尚未在中国汉族人群中得到证实。在这项研究中，我们评估了中国汉族人群中LRP1B中rs61070260与MM风险之间的关系，涉及739名MM患者和592名健康对照。结果表明，LRP1B中rs61070260与MM易感性显著相关（P=3.937×10-37）。此外，rs61070260的连锁不平衡（LD）分析显示，LRP1B基因的26、27和28外显子包含一个LD块，随后的测序分析在LRP1B基因的26和28外显子中鉴定出三个snp （rs762074421、rs756168629、rs113600691）。根据中国百万组数据库和基因组聚集数据库（EAS），在中国人群中未发现导致LRP1B蛋白1661位精氨酸向组氨酸转变的26外显子SNP rs756168629错义突变，该突变通过SIFT和PolyPhen预测为有害或破坏性突变。这些发现确定了LRP1B在MM易感性中的作用。此外，在MM个体中检测到的LRP1B中一个罕见的编码突变（p.R1661H）被认为对编码的蛋白有害，该蛋白被定性为候选肿瘤抑制因子；因此，LRP1B可能是一种与MM的发生和进展有关的疾病相关基因。
Multiple myeloma (MM) is an extremely complex plasma cell malignancy that is genetically heterogeneous. A recent Genome-wide association study (GWAS) indicated that variation at 2q22 (rs61070260) influences MM risk. This association has not been validated to date in a Chinese Han population. In this study, we evaluated the association between rs61070260 in LRP1B and MM risk in a Chinese Han population involving 739 MM patients and 592 healthy controls. Our results indicated that rs61070260 in LRP1B was significantly associated with MM susceptibility (P=3.937×10-37). Furthermore, the linkage disequilibrium (LD) analysis of rs61070260 revealed an LD block encompassing exons 26, 27 and 28 of the LRP1B gene, and a subsequent sequencing analysis identified three SNPs (rs762074421, rs756168629, rs113600691) in exons 26 and 28 of LRP1B. For the SNP rs756168629 in exon 26, a missense mutation which results in a transition from arginine to histidine at position 1661 of the LRP1B protein, has not been found in Chinese populations according to the Chinese Millionome Database and Genome Aggregation Database (EAS), and this mutation was predicted to be deleterious or damaging by SIFT and PolyPhen. These findings firmly establish the role of LRP1B in contributing to MM susceptibility. In addition, the identification of a rare coding mutation (p.R1661H) in LRP1B detected in MM individuals was suggested to be harmful to the encoded protein, which was characterized as a candidate tumour suppressor; thus, LRP1B is likely to be a disease-associated gene that is implicated in the development and progression of MM.