Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects
Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects
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DOI：
10.1248/bpb.25.1356
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发表时间：
2002-10-01
影响因子：
2
通讯作者：
Okumura, K
中科院分区：
文献类型：
--
作者：
Moriya, Y;Nakamura, T;Okumura, K
在本研究中，我们研究了是否在ATP结合盒（ABC）转运基因，MDR 1，MRP 1和MRP 2的多态性，与各自的mRNA表达水平在十二指肠上皮细胞的13名健康日本志愿者。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）或直接测序法检测MDR 1基因型T-129 C、G2677（A，T）和C3435 T，MRP 1基因型G128 C、C218 T、G2168 A和G3173 A，MRP 2基因型C-24 T、G1249 A、C2302 T、C2366 T和G4348 A。MDR 1基因T-129 C、G2677（A，T）和C3435 T突变的等位基因频率分别为2/26、16/26和12/26。MRP 1基因G2168 A突变和MRP 2基因C-24 T突变的等位基因频率分别为1/26和6/26，而其他突变在MRP 1和MRP 2基因中未检测到。相对浓度（平均值+/-S.E.）在C/C-3435、C/T-3435和T/T-3435受试者中，MDR 1 mPNA与绒毛蛋白mRNA的比值分别为0.38 ± 0.15、0.56 ± 0.14和1.13 ± 0.42，这支持在3435位突变T等位基因受试者中单次口服地高辛后的血清浓度较低。3435和2677位点之间存在遗传协作，G/G（2677）、G/（A，T）（2677）和T/（A，T）（2677）位点的遗传协作分别为0.16+/-0.05，1.10 +/-0.40，0.63 +/-0.16（p = 0.107）。然而，MRP 1基因的G2168 A或MRP 2基因的C-24 T对MRP 1或MRP 2 mRNA的相对浓度分别没有显著影响。
In the present study, we examined whether polymorphisms in the ATP-binding cassette (ABC) transporter genes, MDR1, MRP1 and MRP2, were associated with their respective mRNA expression levels in duodenal enterocytes of 13 healthy Japanese volunteers. MDR1 genotypes of T-129C, G2677(A,T) and C3435T, MRP1 genotypes of G128C, C218T, G2168A and G3173A, and MRP2 genotypes of C-24T, G1249A, C2302T, C2366T and G4348A were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or direct sequencing. Mutations T-129C, G2677(A,T) and C3435T of MDR1 gene were found at allele frequencies of 2/26, 16/26 and 12/26, respectively. Mutations G2168A of the MRP1 gene and C-24T of the MRP2 gene were also found at allele frequencies of 1/26 and 6/26, respectively, whereas other mutations were not detected in MRP1 and MRP2 genes. The relative concentrations (mean+/-S.E.) of MDR1 mPNA to villin mRNA were 0.38+/-0.15, 0.56+/-0.14 and 1.13+/-0.42 in the subjects with C/C-3435, C/T-3435 and T/T-3435, respectively, which supported the lower serum concentrations of digoxin after single oral administration in the subjects with the mutant T-allele at position 3435. Genetic collaboration between positions 3435 and 2677 was suggested, and those in G/G(2677), G/(A,T)(2677) and T/(A,T)(2677) were 0.16+/-0.05, 1.10+/-0.40, and 0.63+/-0.16, respectively (p = 0.107). However, there was no remarkable effect of the G2168A of the MRP1 gene or of C-24T of the MRP2 gene on the relative MRP1 or MRP2 mRNA concentrations, respectively.