ABCMdb

PMID: 17225463

Ryu HC, Kwon HY, Choi IK, Rhee DK
Analyses of single nucleotide polymorphisms and haplotype linkage of the human ABCB1 (MDR1) gene in Korean.
Arch Pharm Res. 2006 Dec;29(12):1132-9., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCB1 p.Thr1236Cys The frequcies of the SNPs were C3435T (47.7%), G2677T (37.6%), G2677A (4.4%), T1236C (21.7%), T129C (8%), A2956G (2.5%), T307C (1.5%), A41aG (92%), C145G (0%), and G4030C (0 %). Login to comment 44 ABCB1 p.Thr1236Cys Eleven haplotypes were detected in pairwise of 3 SNPs (T1236C, G2677T/A, C3435T) using Haplotype analyses. Login to comment 53 ABCB1 p.Thr1236Cys The allele frequencies of the 9 MDR1 SNPs and the sample numbers were C3435T 47.7% (n=500), G2677T 37.6% (n=500), G2677A 4.4% (n=500), T1236C 21.7% (n=500), A41aG 9.2% (n=388), T129C 8% (n=lO0), A2956G 2.5% (n=lO0), and T307C 1.5% (n=lO0). Login to comment 55 ABCB1 p.Thr1236Cys There were 4 point mutations (T307C, G2677T/A, and A2956G) among the 9 SNPs that caused an amino acid exchange in MDR1, but not the others (C3435T, T1236C, A41aG, T129C, C-145G, and G4030C) (Table II). Login to comment 58 ABCB1 p.Met986Val In addition, two non-coding SNPs in the Korean TableI1.Positions,sequences,and frequenciesof the MDR1variantsin the KoreangenomicDNA MDR1 Analyzed Genotype,N Exon/Position Effect individuals,N GenomicDNA Allelefrequency(%) W/W WN VN W V A-41aG 5'-flanking/-41 Noncoding 388 320(NA) 66(NG) C-145G la/-145 Noncoding 100 100(C/C) 0 (C/G) T-129C lb/-129 Noncoding 100 84(T/T) 16(T/C) T-307C 5/307 Phel03Leu 100 97(T/T) 3 (T/C) T-1236C 12/1236 Gly412Gly 500 330(T/T) 123(T/C) G-2677T 21/2677 Ata893Ser 500 166G/G) 208(G/T) G-2677A 21/2677 Ala893Thr 500 40(G/A) 4 (NT) A-2956G 24/2956 Met986Val 100 95(NA) 5(NG) C-3435T 26/3435 Ile114511e 500 112(C/C) 299(C/T) G4030C 28/4030 Noncoding 100 100(G/G) 0(G/C) 2 (G/G) 91 (A) 9.2 (G) 0 (G/G) 100 (C) 0 (G) 0 (C/C) 92 (T) 8 (C) 0 (C/C) 98.5 (m) 1.5 (C) 47 (C/C) 78.3 (T) 21.7 (C) 82 (T/T) 58 (G) 37.6 (m) 0 (NA) 4.4 (A) 0 (G/G) 97.5 (A) 2.5 (G) 89 (T/T) 52.3 (C) 47.7 (T) 0 (C/C) 100(G) 0 (C) * PCR-RFLP-basedgenotypingwas developedto detectthe newand knownvariationsusing are presentedas (exon+/-n),i.e.,n nucleotidesupstream(-) or downstream(+) of theexons. Login to comment 65 ABCB1 p.Thr1236Cys Haplotype and LD analysis The most frequent 3 SNPs (T1236C, G2677T/A, C3435T) were further analyzed for their haplotype. Login to comment 66 ABCB1 p.Thr1236Cys The frequency of the 11 haplotypes in T1236C-G2677T/A-C3435T loci were T-G-C (28.1%), T-T-T (25.1%), C-G-C (14.2%), T-GT (14.1%), T-T-C (7.6%), C-T-T (4.3%), C-A-C (2.1%), TA-C (1.9%), C-G-T (1.6%), C-T-C (0.6%), and T-A-T (0.4%). Login to comment 71 ABCB1 p.Thr1236Cys C3435T SNP was shown to have relationship with the T1236C (D' value of 0.64), T129C (D' value of 0.58), A41aG (D' value of 0.32), and G2677T (D' value of 0.37) SNPs. Login to comment 73 ABCB1 p.Thr1236Cys ABCB1 p.Thr1236Cys ABCB1 p.Thr1236Cys ABCB1 p.Thr1236Cys This suggests that C3435T SNP has some relationship with the other 4 SNPs, whereas the G2677T SNP has a relationship with A41aG T129C T1236C G2677T C3435T A41aG T129C 0.19 T1236C 0.17 G2677T 0.14 C3435T 0.32* 0.05 0.58* 0.06 0.58* 0.64* 0.37* T129C T1236C G2677T C3435T A41aG T129C T1236C G2677T Fig. 2. Login to comment 79 ABCB1 p.Thr1236Cys DISCUSSION In this study, the frequencies of 3 SNPs from 500 samples showed that C3435T (47.7%) was the most frequent followed by G2677T (37.6%), and T1236C (21.7%). Login to comment 80 ABCB1 p.Thr1236Cys In contrast, Yi et aL (2004) reported that T1236C was the most frequent (38.1%) followed by G2677T Table t|i. Login to comment 97 ABCB1 p.Thr1236Cys The 3rd most frequent SNP, T1236C SNP, detected at the exon 12, which affected the expression and function of P-gp (Marzolini et al., 2004; Kim et al., 2001; Goto et al., 2002; IIImer et al., 2002), was similar to those reported in other Asian populations (Japanese, Chinese, Indian, Malay) but much higher than those reported in Caucasians (34-41%) and Africans (15%) (Table III). Login to comment 98 ABCB1 p.Thr1236Cys When the LD for all pairs of exons 12, 21, and 26 (3 SNPs T1236C, G2677T/A, and C3435T) were examined, of the 12 possible haplotypes, 11 and 12 were observed in the Korean and Chinese subjects, respectively (Zhang et al., 2005), and these haplotype numbers were much larger than those in western black Africans (6 haplotypes; Allabi et al., 2005), Benineses (8 haplotypes), African-Americans (8 haplotypes), Caucasians (10 haplotypes) (Kroetz et al., 2003; Allabi et al., 2005), Malays (6 haplotypes), Chinese (10 haplotypes), and Indians (9 haplotypes; Tang et al., 2002). Login to comment 115 ABCB1 p.Thr1236Cys Two synonymous SNPs (T1236C and C3435T) and a non-synonymous SNP (G2677T, Ala893Ser) were found to be linked in 62% of European Americans and 13% of African Americans (Kim et al., 2001; Goto et al., 2002; IIImer et al., 2002). Login to comment 116 ABCB1 p.Thr1236Cys This study also confirmed this similar linkage in Koreans, and the T1236C was linked to an exon 26 (C3435T) and exon 21 (G2677T) SNPs in 64% and 37% of cases, relatively. Login to comment 120 ABCB1 p.Thr1236Cys A LD was also found in the C3435T SNP with T129C, and T1236C. Login to comment