MDR1 SNPs Affect The Occurrence And Prognosis Of Diffuse Large B-cell Lymphoma

PurposeMDR1 is a member of the adenosine triphosphate(ATP)binding cassette(ABC)transporter of the MDR/TAP subfamily and associated wth disease development.We investigated whether the MDR1(multidrug resistance 1)gene single nucleotide polymorphism(SNP)and haplotype variants were associated with the susceptibility to diffuse large Bcell lymphoma(DLBCL).MethodsA total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study.They were genotyped by polymerase chain reaction-allele specific primers(PCR-ASP)method or DNA direct sequencing at three common loci:C1236T,G2677T/A and C3435T.ResultsAt locus G2677T/A,allele G and genotype GT were significantly more common in DLBCL(G:OR=1.48,95%CI 1.08-2.02,Pc=0.03;GT:OR=1.96,95%CI 1.25-3.07,Pc<0.01),while genotype AT in this locus seemed to be protective(OR=0.29,95%CI 0.02-0.72,Pc=0.03).TT genotype at locus C3435T showed a risk factor in DLBCL(OR=2.38,95%CI 1.52-3.74,Pc<0.01).The frequency of T-G-T haplotype was significantly increased in DLBCL group(OR=5.21,95%CI 2.58-10.54,Pc<0.01);haplotype of G-Tin 2677-3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group(G-T:OR=3.97,95%CI 2.31-6.85,Pc<0.01;2677GT/3435TT:OR=4.55,95%CI 2.02-10.22,Pc<0.01).ConclusionsOur findings demonstrate that G,GT at locus G2677T/A,and TT at locus C3435T might contribute to the susceptibility to DLBCL,as well as haplotype of T-G-T,G-Tin 2677-3435and diplotype of 2677GT/3435TT,while AT at locus G2677T/A mightbe a protective genotype.These findings could provide evidencethat the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.PurposeMDR1(multidrug resistance 1)encodes an adenosine triphosphate(ATP)dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health.The present study was aimed toinvestigate whether the MDR1 gene single nucleotide polymorphisms(SNPs)were associated with the prognosis of diffuse large B-cell lymphoma(DLBCL).MethodsThree common SNPs,including C1236T,G2677T/A and C3435T were focused on and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele specific primers(PCR-ASP)method or DNA direct sequencing.ResultsAt locus C1236T,patients carrying T allele(genotype CT and TT)had a prolonged overall survival(OS)when compared with patients with CC genotype(2-year OS 82.6%vs.60.0%,respectively;HR=0.1,95%CI 0.01-0.6,p=0.016).At locus C3435T,complete remission/complete remission unconfirmed(CR/CRu)ratein C allele group was significantly higher than T allele group(66.7%vs.51.9%,respectively;p=0.009).The progression-free survival(PFS)curves of with T(genotype CT and TT)and without T(genotype CC)were significantly different(2-year PFS 46.4%in with T group vs.73.7%in without T group,respectively;HR=1.9,95%CI 1.0-3.6,p=0.045).At locus G2677T/A,the age for genotypes AG and AT groups were significantly younger than the other genotypes(51.1 ± 12.6 years vs.57.7± 13.4 years,respectively;p=0.033).In the haplotype analysis of loci 1236-3435,compared with T-C group,the C-T group displayed aninferiorPFS rate(2-year PFS 23.0%vs.50.6%,respectively;HR=7.8,95%CI 1.9-32.6,p=0.005),while C-C and T-T groups showed an intermediate PFS rate.ConclusionsOur findings demonstrate that genotype CT+TT at locus C1236T,allele C and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL,as well as haplotype of T-C in loci 1236-3435.Besides,genotypes at locus G2677T/A might affect age at diagnosis,which has important prognostic value for DLBCL.