Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort

Y Toyoda, A Mancikova, V Krylov, K Morimoto, K Pavelcova, J Bohata, K Pavelka, M Pavlikova, H Suzuki, H Matsuo, T Takada, B Stiburkova

. 2019 ; () : 8(4).

Jazyk angličtina Země Švýcarsko

Perzistentní odkaz   https://www.medvik.cz/link/bmc21027467

Grantová podpora
NV15-26693A MZ0 CEP - Centrální evidence projektů

ATP-binding cassette subfamily G member 2 (ABCG2) is a physiologically important urate transporter. Accumulating evidence demonstrates that congenital dysfunction of ABCG2 is an important genetic risk factor in gout and hyperuricemia; recent studies suggest the clinical significance of both common and rare variants of ABCG2. However, the effects of rare variants of ABCG2 on the risk of such diseases are not fully understood. Here, using a cohort of 250 Czech individuals of European descent (68 primary hyperuricemia patients and 182 primary gout patients), we examined exonic non-synonymous variants of ABCG2. Based on the results of direct sequencing and database information, we experimentally characterized nine rare variants of ABCG2: R147W (rs372192400), T153M (rs753759474), F373C (rs752626614), T421A (rs199854112), T434M (rs769734146), S476P (not annotated), S572R (rs200894058), D620N (rs34783571), and a three-base deletion K360del (rs750972998). Functional analyses of these rare variants revealed a deficiency in the plasma membrane localization of R147W and S572R, lower levels of cellular proteins of T153M and F373C, and null urate uptake function of T434M and S476P. Accordingly, we newly identified six rare variants of ABCG2 that showed lower or null function. Our findings contribute to deepening the understanding of ABCG2-related gout/hyperuricemia risk and the biochemical characteristics of the ABCG2 protein.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21027467
003      
CZ-PrNML
005      
20220404160309.0
007      
ta
008      
211029s2019 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/cells8040363 $2 doi
035    __
$a (PubMed)31003562
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Toyoda, Yu $u Toyoda, Yu. Department of Pharmacy, The University of Tokyo Hospital, Tokyo 113-8655, Japan. ytoyoda-tky@umin.ac.jp.
245    10
$a Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort / $c Y Toyoda, A Mancikova, V Krylov, K Morimoto, K Pavelcova, J Bohata, K Pavelka, M Pavlikova, H Suzuki, H Matsuo, T Takada, B Stiburkova
520    9_
$a ATP-binding cassette subfamily G member 2 (ABCG2) is a physiologically important urate transporter. Accumulating evidence demonstrates that congenital dysfunction of ABCG2 is an important genetic risk factor in gout and hyperuricemia; recent studies suggest the clinical significance of both common and rare variants of ABCG2. However, the effects of rare variants of <ovid:i>ABCG2</ovid:i> on the risk of such diseases are not fully understood. Here, using a cohort of 250 Czech individuals of European descent (68 primary hyperuricemia patients and 182 primary gout patients), we examined exonic non-synonymous variants of <ovid:i>ABCG2</ovid:i>. Based on the results of direct sequencing and database information, we experimentally characterized nine rare variants of ABCG2: R147W (rs372192400), T153M (rs753759474), F373C (rs752626614), T421A (rs199854112), T434M (rs769734146), S476P (not annotated), S572R (rs200894058), D620N (rs34783571), and a three-base deletion K360del (rs750972998). Functional analyses of these rare variants revealed a deficiency in the plasma membrane localization of R147W and S572R, lower levels of cellular proteins of T153M and F373C, and null urate uptake function of T434M and S476P. Accordingly, we newly identified six rare variants of ABCG2 that showed lower or null function. Our findings contribute to deepening the understanding of <ovid:i>ABCG2</ovid:i>-related gout/hyperuricemia risk and the biochemical characteristics of the ABCG2 protein.
650    02
$a ABC transportér z rodiny G, člen 2 $x genetika $x metabolismus $7 D000070997
650    02
$a mladiství $7 D000293
650    02
$a dospělí $7 D000328
650    02
$a senioři $7 D000368
650    02
$a senioři nad 80 let $7 D000369
650    02
$a biologický transport $7 D001692
650    02
$a dítě $7 D002648
650    02
$a předškolní dítě $7 D002675
650    02
$a kohortové studie $7 D015331
650    02
$a běloši $x genetika $7 D044465
650    02
$a ženské pohlaví $7 D005260
650    02
$a genetická predispozice k nemoci $7 D020022
650    02
$a dna (nemoc) $x genetika $x krev $x metabolismus $7 D006073
650    02
$a HEK293 buňky $7 D057809
650    02
$a lidé $7 D006801
650    02
$a hyperurikemie $x genetika $x krev $7 D033461
650    02
$a mužské pohlaví $7 D008297
650    02
$a lidé středního věku $7 D008875
650    02
$a nádorové proteiny $7 D009363
650    02
$a přenašeče organických aniontů $7 D027361
650    02
$a jednonukleotidový polymorfismus $7 D020641
650    02
$a kyselina močová $x krev $7 D014527
651    _2
$a Česká republika $7 D018153
700    1_
$a Mančíková, Andrea $u Department of Cell Biology, Faculty of Science, Charles University, 128 00 Prague 2, Czech Republic $7 xx0279626
700    1_
$a Krylov, Vladimír $7 xx0128644 $u Department of Cell Biology, Faculty of Science, Charles University, 128 00 Prague 2, Czech Republic
700    1_
$a Morimoto, Keito
700    1_
$a Pavelcová, Kateřina $7 xx0228018 $u Institute of Rheumatology, 128 50 Prague 2, Czech Republic
700    1_
$a Bohatá, Jana $u Institute of Rheumatology, 128 50 Prague 2, Czech Republic
700    1_
$a Pavelka, Karel, $d 1954- $7 jn99240000847 $u Institute of Rheumatology, 128 50 Prague 2, Czech Republic
700    1_
$a Pavlíková, Markéta, $d 1975- $7 xx0093283 $u Department of Probability and Mathematical Statistics, Faculty of Mathematics and Physics, Charles University, 121 16 Prague 2, Czech Republic
700    1_
$a Suzuki, Hiroshi
700    1_
$a Matsuo, Hirotaka
700    1_
$a Takada, Tapie
700    1_
$a Stibůrková, Blanka, $d 1970- $7 xx0056517 $u Institute of Rheumatology, 128 50 Prague 2, Czech Republic ; Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, 121 08 Prague 2, Czech Republic
773    0_
$t Cells $x 2073-4409 $g (2019), s. 8(4) $p Cells $w MED00194911
773    0_
$p Cells $g 8(4), 2019 04 18 $x 2073-4409
910    __
$a ABA008 $y p $b sig $z 0
990    __
$a 20211029084328 $b ABA008
991    __
$a 20220404160307 $b ABA008
999    __
$a ok $b bmc $g 1716617 $s 1147988
BAS    __
$a 3
BMC    __
$a 2019 $d 8(4) $x MED00194911 $i 2073-4409 $m Cells
GRA    __
$a NV15-26693A $p MZ0
LZP    __
$a 2021-granty

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace