ABCMdb

PMID: 24441388

Matsuo H, Nakayama A, Sakiyama M, Chiba T, Shimizu S, Kawamura Y, Nakashima H, Nakamura T, Takada Y, Oikawa Y, Takada T, Nakaoka H, Abe J, Inoue H, Wakai K, Kawai S, Guang Y, Nakagawa H, Ito T, Niwa K, Yamamoto K, Sakurai Y, Suzuki H, Hosoya T, Ichida K, Shimizu T, Shinomiya N
ABCG2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload.
Sci Rep. 2014 Jan 20;4:3755. doi: 10.1038/srep03755., [PubMed]

Sentences

No. Mutations Sentence Comment

17 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Their functional ABCG2 activities were estimated from their genotype combinations of its two dysfunctional missense variants, Q126X (rs72552713) and Q141K (rs2231142). Login to comment 18 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Because there is no simultaneous presence of the minor alleles of non-functional variant Q126X and half-functional variant Q141K in one hap- lotype5,7 , we defined three haplotype IDs as *1, *2, and *3, as shown in Figure 1a. Login to comment 24 ABCG2 p.Gln126* Furthermore, Q126X homozygote signifying complete deficiency of ABCG2 was identified in one case with gout in the ROL hyperuricemia group. Login to comment 26 ABCG2 p.Gln141Lys ABCG2 p.Gln126* When hyperuricemia was divided into three distinct types (i.e., RUE type, combined type, and ROL type as shown in Supplementary Fig. S1), severe ABCG2 dysfunction (#1/4 function) significantly raised the risk of combined and ROL types but not that of RUE type Figure 1 | Estimation of ABCG2 function from diplotype of Q126X and Q141K alleles. Login to comment 27 ABCG2 p.Gln141Lys ABCG2 p.Gln126* (a) ABCG2*2 or *3 represents a haplotype with Q141K or Q126X variant, respectively. Login to comment 28 ABCG2 p.Gln141Lys ABCG2 p.Gln126* ABCG2*1 indicates a haplotype with neither Q141K nor Q126X variant. Login to comment 29 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Since Q141K is a half-functional variant and Q126X is a nonfunctional variant, relative function of ABCG2*1, *2, and *3 is 1, 1/2, and 0, respectively, which is visualized by black-indicated areas. Login to comment 32 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln126* ABCG2 p.Gln126* Table 1 | ABCG2 functions of participants Estimated transport activity Diplotype of Q126X (rs72552713) and Q141K (rs2231142) alleles** Case{ Control N % N % #1/4 function *3/*3 or *2/*3 29 (26) 4.5 (4.7) 22 1.3 1/2 function *1/*3 or *2/*2 151 (135) 23.4 (23.5) 190 11.7 3/4 function *1/*2 307 (277) 47.7 (48.2) 600 37.0 Full function *1/*1 157 (136) 24.4 (23.7) 811 50.0 Total 644 (575) 100.0 (100.0) 1,887 100.0 **Haplotypes ''Q-Q``, ''Q-K``, and ''X-Q`` of two SNPs (Q126X and Q141K) are referred to as *1, *2, and *3, respectively. Login to comment 33 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Risk alleles are X for Q126X, and K for Q141K. Login to comment 67 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Genotyping of ABCG2 Q126X (rs72552713) and Q141K (rs2231142) was performed by high-resolution melting analysis with a LightCycler 480 (Roche Diagnostics)19 . Login to comment 68 ABCG2 p.Gln141Lys ABCG2 p.Gln126* From the haplotype analyses reported in the previous studies5,7 , there is no simultaneous presence of the minor alleles (risk alleles) of non-functional variant Q126X and half-functional variant Q141K in one haplotype. Login to comment 69 ABCG2 p.Gln141Lys ABCG2 p.Gln126* In this study, their haplotype IDs, *1, *2, and *3, were defined as Figure 1a; the combination of wild-type Q126X and Q141K alleles (''Q-Q``) was designated as ABCG2*1, which corresponds to the cDNA sequence of GenBank (accession number NM_004827). Login to comment 71 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Based on the diplotype of Q126X and Q141K alleles (Fig. 1b)5,7 , ABCG2 function was estimated and divided into four groups5-7 ; i.e., full function, 3/4 function, 1/2 function, and #1/4 function (Table 1). Login to comment