Polymorphisms Are Associated with Multiple Myeloma Risk in a Chinese Han Population.

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.