Li Bingjie, Liu Chenxi, Cheng Guixue, Peng Mengle, Qin Xiaosong, Liu Yong, Li Yongzhe, Qin Dongchun
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan Province, Zhengzhou 450052, Henan , P.R. China.
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P.R.China.
J Cancer. 2019 Jan 1;10(3):577-582. doi: 10.7150/jca.28905. eCollection 2019.
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 and MM risk in a Chinese Han population involving 739 MM patients and 592 healthy controls. Our results indicated that rs61070260 in was significantly associated with MM susceptibility (P=3.937×10). Furthermore, the linkage disequilibrium (LD) analysis of rs61070260 revealed an LD block encompassing exons 26, 27 and 28 of the gene, and a subsequent sequencing analysis identified three SNPs (rs762074421, rs756168629, rs113600691) in exons 26 and 28 of . 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 in contributing to MM susceptibility. In addition, the identification of a rare coding mutation (p.R1661H) in detected in MM individuals was suggested to be harmful to the encoded protein, which was characterized as a candidate tumour suppressor; thus, is likely to be a disease-associated gene that is implicated in the development and progression of MM.
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）处的变异会影响MM风险。迄今为止，该关联在中国汉族人群中尚未得到验证。在本研究中，我们评估了中国汉族人群中rs61070260与MM风险之间的关联，该人群包括739例MM患者和592例健康对照。我们的结果表明，rs61070260与MM易感性显著相关（P = 3.937×10）。此外，rs61070260的连锁不平衡（LD）分析揭示了一个包含LRP1B基因第26、27和28外显子的LD区域，随后的测序分析在LRP1B基因的第26和28外显子中鉴定出三个单核苷酸多态性（SNP，rs762074421、rs7561686,29、rs113600691）。对于第26外显子中的SNP rs756168,29，根据中国百万基因组数据库和基因组聚合数据库（EAS），在中国人群中尚未发现导致LRP1B蛋白第1661位精氨酸向组氨酸转变的错义突变，并且该突变被SIFT和PolyPhen预测为有害或具有破坏性。这些发现有力地证实了LRP1B在MM易感性中的作用。此外，在MM个体中检测到的LRP1B中罕见的编码突变（p.R1661H）被认为对编码蛋白有害，该蛋白被表征为候选肿瘤抑制因子；因此，LRP1B可能是一个与疾病相关的基因，参与MM的发生和发展。
