Candidate Gene Association Analysis Of Multiple Myeloma In Chinese Han Population

BackgroundMultiple myeloma(MM)is an incurable malignancy of mature B-lymphoid cells,and its pathogenesis is only partially understood.Previous studies have demonstrated that a number of Non-Hodgkin Lymphoma(NHL)associated genes also show susceptibility to MM,suggesting malignancies originating from B cells may share similar genetic susceptibility.Follicular lymphoma(FL)and diffuse large B-cell lymphoma(DLBCL)are two common histological subtypes of NHL.Multiple genome-wide association studies(GWASs)of NHL have identified several susceptibility loci,including HLA-I,HLA-II,CXCR5,ETS1,LPP and NCOA1 genes,but whether these genes confer susceptibility to MM in Chinese Han population remain to be studied.ObjectiveThis aim of our study is to investigate the relationship between HLA–I(rs6457327),HLA–II(rs2647012 and rs7755224),CXCR5(rs4938573),ETS1(rs4937362),LPP(rs6444305)and NCOA1(rs79480871)and MM in the Chinese Han population,also the relationship between these loci and clinical indices of MM.MethodsThe current study was designed as a case–control study.827 MM cases and 709 healthy controls of Chinese Han were collected and all subjects were unrelated and self-reported as Han Chinese ethnicity.Seven single nucleotide polymorphisms(SNPs)in the HLA–I region(rs6457327),the HLA–II region(rs2647012 and rs7755224),the CXCR5 gene(rs4938573),the ETS1 gene(rs4937362),the LPP gene(rs6444305),and the NCOA1 region(rs79480871)were genotyped by using the Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry(MALDI-TOF MS).ResultsFor the NCOA1 gene,the genotype and allele frequencies of rs79480871 manifested associations with MM patients(pa=3.5×10-4 and pa=1.5×10-4).For the HLA-I region,the rs6457327 genotype was more readily associated with MM patients than with controls(pa=4.9×10-3).Significant associations were observed in MM patients for rs79480871 in NCOA1 gene region in the additive and dominant models(pa=1.1×10-4 and pa=2.1×10-4).For rs6457327 in the HLA-I region,an association was observed in the dominant model(pa=0.03).In the recessive model,a weak association was observed for rs4937362 in the EST1 gene(pa=0.048).No association was found between these SNPs and the clinical index of MM(p>0.05).ConclusionNCOA1 might be a novel susceptibility gene for MM patients in the Chinese Han population.NCOA1 might act as a common genetic factor in the pathogenesis of MM and NHL.