IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Comparative study of single nucleotide polymorphisms (SNPs) in the exon 28 of the VWF between healthy donors, VWD2M (with p.E1549K and p.R1374C) and VWD2B patients (with p.R1308C and p.V1316M) in a single center in Argentina. Preliminary report.
Autor/es:
WOODS AI ; CASINELLI MM; PAIVA J; SANCHEZ LUCEROS A; KEMPFER AC; LAZZARI MA
Lugar:
Dublin
Reunión:
Congreso; Congreso de ISTH; 2018
Institución organizadora:
ISTH
Resumen:
Comparative study of singlenucleotide polymorphisms (SNPs) in the exon28 of the VWF between healthy donors,VWD2M (with p.E1549K and p.R1374C) and VWD2B patients (with p.R1308C and p.V1316M)in a single center in Argentina. Preliminary report. Woods AI1,Paiva J2, Kempfer AC1, Sanchez-Luceros A1,2,Lazzari MA1. 1Laboratorio de Hemostasia y Trombosis,IMEX-CONICET-ANM, 2Instituto de Investigaciones Hematológicas,Academia Nacional de Medicina de Buenos Aires, CABA, Argentina Background:Theinfluence of different SNPs on VWF survival between different ethnic and racialgroups was described. This makes it necessary to better characterize the ethnicand racial variations in the VWFgene, resulting in ambiguity or erroneous conclusions that may have an impacton the diagnosis of VWD. SNPs p.V1565L and p.G1643S were associated with higherproteolysis by ADAMTS13, while p.D1472H, p.Q1571H and p.P1601T, resistance toproteolysis. Aim:We describethe allelic frequencies (AFs) of SNPs in the exon 28 with high frequency innormal population or causing altered proteolysis, in healthy donors and in VWD2Mpatients (P) with p.E1549K and p.R1374C, and VWD2B P and p.R1308C and p.V1316M, the mostfrequent mutations in these VWD variants in our Center. In VWD P,we compare SNP presence with propeptide/VWF:Ag (VWFpp ratio), useful to measureVWF survival. Materials and methods:Healthy donors: 208 alleles. VWFppratio=0.9-2.14.VWD2M P: with p.E1549K (32 alleles): VWFpp ratio=1.9±0.6(43.7% with high values); with p.R1374C (32 alleles): VWFpp ratio=2.5±1.0 (69.2% with high values). VWD2B P: with p.R1308C (16 alleles): VWFpp ratio=2.3±0.7 (62.5% with high values); with p.V1316M (24 alleles): VWFpp ratio=2.2±0.6 (54.5% with high values).SNPs within exon 28 of VWF gene were analyzed and the AFs were compared with thosereported in ISTH-SSC VWF Online Database. Results:Our results are shown in the table 1.Donors: the AFs of the SNP were similar as those reportedin the VWF Database. Only p.A1555 showed higher AF than that reported.VWD P: p.Q1571 H, p.P1601T and p.G1643S showed thesame allelic frequency as our donors and those reported in the VWF Database.VWD2M P showed an increase of 1472H allele, whileVWD2B P showed an increment of 1565L allele. Conclusions:There were no significant differences in AFs of SNP inexon 28 between our donors and those worldwide, as reported in the VWF Database.Differences in AFs seen in our VWD P together the associatedmutations could be responsible for variations in VWF survival in P. Table 1. Allelic frequency of SNP in our normals andVWD patients. SNP VWD 2M p.E1549K p.R1374C VWD 2B p.V1316M p.R1308C healthy donors Our population ISTH report Source population A1381T AF g/a 0.87/0.13 0.68/0.32 0.55/0.45 0.93/0.07 0.62/0.38 North american: 0.65/0.35 British: 0.54/0.46 Japanese: 0.59/0.41 D1472H AF g/c 0.4/0.6 0.54/0.46 0.94/0.05 1/0 0.84/0.16 North american: 0.89/0.11 T1547 AF c/t 0.81/0.19 0.68/0.32 0.79/0.21 0.93/0.07 0.66/0.34 British: 0.58/0.42 Japanese: 0.59/0.41 A1555 AF a/c 1/0 1/0 0.66/0.34 0.64/0.36 0.91/0.09 Japanese: 0.64/0.36 V1565L AF g/t 1/0 1/0 0.66/0.34 0.71/0.29 0.90/0.10 European: 0.92/0.08 Q1571H AF g/c 1/0 1/0 1/0 1/0 1/0 French: 0.99/0.01 P1601T AF c/a 1/0 1/0 1/0 1/0 1/0 Mexican: 0.97/0.03 G1643S AF g/a 1/0 1/0 1/0 1/0 1/0 French 0.99/0.01