The 10 references with contexts in paper R. Kazakov E., V. Evteev A., O. Muslimova V., I. Mazerkina A., E. Demchenkova Yu., E. Shikh V., Р. Казаков Е., В. Евтеев А., О. Муслимова В., И. Мазеркина А., Е. Демченкова Ю., Е. Ших В. (2018) “Перспективы использования полиморфизма C3435T гена P-гликопротеина ABCB1 в персонализированной медицине // Prospects of using C3435T polymorphism in the ABCB1 gene encoding P-glycoprotein in personalised medicine” / spz:neicon:vedomostincesmp:y:2017:i:4:p:212-220

1
Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomics to mechanism. Oncogene 2003; 22(47): 7468–85.
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    Äâå ãîìîëîãè÷íûå äðóã äðóãó è ñèììåòðè÷íî ðàñïîëîæåííûå àìèíîêèñëîòíûå ïîñëåäîâàòåëüíîñòè ôîðìèðóþò ïî 6 òðàíñìåìáðàííûõ äîìåíîâ è ïî 1 äîìåíó ñ ÀÒÔàçíîé àêòèâíîñòüþ, ôîðìèðóÿ â ìåìáðàíå ïîðó (èç 12 òðàíñìåìáðàííûõ äîìåíîâ)
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    . Ïðè îáñëåäîâàíèè 247 ÷åëîâåê ðàçíîé ýòíè÷åñêîé ïðèíàäëåæíîñòè áûëè âûÿâëåíû 48 ïîëèìîðôèçìîâ ãåíà Ð-ãëèêîïðîòåèíàABCB1, 13 èç êîòîðûõ áûëè ñâÿçàíû ñ èçìåíåíèåì ïåðâè÷íîé ñòðóêòóðû [2]. Íà ðèñóíêå 1 ïîêàçàíû ìåñòà íàèáîëåå ðàñïðîñòðàíåííûõ çàìåí.

2
Kroetz DL, Pauli-Magnus C, Hodges LM, Huang CC, Kawamoto M, Johns SJ, et al. Sequence diversity and haplotype structure in the humanABCB1(MDR1, multidrug resistance transporter) gene. Pharmacogenetics 2003; 13(8): 481–94.
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    äðóã äðóãó è ñèììåòðè÷íî ðàñïîëîæåííûå àìèíîêèñëîòíûå ïîñëåäîâàòåëüíîñòè ôîðìèðóþò ïî 6 òðàíñìåìáðàííûõ äîìåíîâ è ïî 1 äîìåíó ñ ÀÒÔàçíîé àêòèâíîñòüþ, ôîðìèðóÿ â ìåìáðàíå ïîðó (èç 12 òðàíñìåìáðàííûõ äîìåíîâ) [1]. Ïðè îáñëåäîâàíèè 247 ÷åëîâåê ðàçíîé ýòíè÷åñêîé ïðèíàäëåæíîñòè áûëè âûÿâëåíû 48 ïîëèìîðôèçìîâ ãåíà Ð-ãëèêîïðîòåèíàABCB1, 13 èç êîòîðûõ áûëè ñâÿçàíû ñ èçìåíåíèåì ïåðâè÷íîé ñòðóêòóðû
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    . Íà ðèñóíêå 1 ïîêàçàíû ìåñòà íàèáîëåå ðàñïðîñòðàíåííûõ çàìåí. Ïðåäñòàâëåííûå äàííûå ñâèäåòåëüñòâóþò î òîì, ÷òî îáû÷íî îíè ëîêàëèçîâàíû â öèòîïëàçìàòè÷åñêîì ïðîñòðàíñòâå è ìîãóò âëèÿòü íà ñóáñòðàòíóþ ñïåöèôè÷íîñòü òðàíñïîðòåðà, êàê ïðàâèëî, â ñòîðîíó ñíèæåíèÿ ñêîðîñòè åãî óäàëåíèÿ èç êëåòêè è/èëè îðãàíèçìà.

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    Ïðè ýòîì ñîäåðæàíèå Ð-ãëèêîïðîòåèíà â äâåíàäöàòèïåðñòíîé êèøêå ó ëèö ñ ãåíîòèïîì 3435ÒÒ áûëî â 2 ðàçà ìåíüøå, ÷åì ó ãîìîçèãîò 3435ÑÑ.  äàëüíåéøåì âëèÿíèþ ïîëèìîðôèçìà ãåíà ABCB1íà ôàðìàêîêèíåòèêó äèãîêñèíà áûëî ïîñâÿÒàáëèöà 1 ×ÀÑÒÎÒÛ ÀËËÅËÅÉ ÃÅÍÀABCB1Ó ÏÐÅÄÑÒÀÂÈÒÅËÅÉ ÐÀÇËÈ×ÍÛÕ ÐÀÑ
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    çàìåíû â ÄÍÊÓ÷àñòîê ãåíà Íóêëåîòèäíàÿ çàìåíà Àìèíîêèñëîòíàÿ çàìåíà* ×àñòîòà ìèíîðíîãî àëëåëÿ ÅâðîïåîèäûÍåãðîèäûÌîíãîëîèäû Ïîëîæåíèå (–274)èíòðîí –1G > A—00,0160 (–60)èíòðîí –1A > T—00,0100 (–41)èíòðîí –1A > G—000,017 –241íåêîä. îáë.

3
Takane H, Kobayashi D, Hirota T, Kigawa J, Terakawa N, Otsubo K, et al. Haplotype-oriented genetic analysis and functional assessment of promoter variants in theMDR1(ABCB1) gene. J Pharmacol Exp Ther. 2004; 311(3): 1179–87.
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    Èçâåñòíî, ÷òî àêòèâèðîâàòü òðàíñêðèïöèþ ãåíàABCB1ñïîñîáíû íåêîòîðûå ñòðåññîâûå àãåíòû: òåïëîâîé øîê, ÷àñòè÷íàÿ ðåçåêöèÿ ïå÷åíè, âîçäåéñòâèå êàíöåðîãåíîâ, õèìèîòåðàïåâòè÷åñêèå ïðåïàðàòû, óëüòðàôèîëåòîâîå è ðåíòãåíîâñêîå èçëó÷åíèå,àâïðîìîòîðå ãåíà èìååòñÿ íåñêîëüêî ïîñëåäîâàòåëüíîñòåé äëÿ ñâÿçûâàíèÿ ôàêòîðîâ òåïëîâîãî øîêà
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    . Ñâåäåíèÿ î ÷àñòîòàõ íàèáîëåå ðàñïðîñòðàíåííûõ àëëåëåé ãåíàABCB1îáîáùåíû â òàáëèöå 1.  ôàðìàêîãåíåòè÷åñêèõ èññëåäîâàíèÿõ íàèáîëüøåå ÷èñëî ðàáîò ïîñâÿùåíî êëèíè÷åñêîé çíà÷èìîñòè òðåõ ïîëèìîðôèçìîâ: C1236T, G2677T/A è C3435T, èç êîòîðûõ òîëüêî îäèí, G2677T/A, ñâÿçàí ñ èçìåíåíèåì ñòðóêòóðû ãëèêîïðîòåèíà.

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Romanov BK. Regulation of myocardial lysosomal enzyme activity by calcium. Biomedical Chemistry 2005; 51(6): 634–42 (in Russian).
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    Àññîöèàöèÿ ïîëèìîðôèçìà C3435T ãåíàABCB1 ñ ðàçâèòèåì íåæåëàòåëüíûõ ëåêàðñòâåííûõ ðåàêöèé Äèãîêñèí Äèãîêñèí — ýòî ñåðäå÷íûé ãëèêîçèä, øèðîêî ïðèìåíÿþùèéñÿ â êëèíè÷åñêîé ïðàêòèêå äëÿ íîðìàëèçàöèè ñåðäå÷íîãî ðèòìà ïðè ïîñòîÿííîé ôîðìå ôèáðèëëÿöèè ïðåäñåðäèé
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    . Ñîâìåñòíîå ïðèìåíåíèå ñ äèãîêñèíîì ËÑ, èíãèáèðóþùèõ Ð-ãëèêîïðîòåèí, íàïðèìåð, êëàðèòðîìèöèíà, õèíèäèíà èëè öèêëîñïîðèíà, ïðèâîäèò ê çíà÷èòåëüíîìó ïîâûøåíèþ êîíöåíòðàöèè äèãîêñèíà â ïëàçìå êðîâè, à ïðèåì ñîâìåñòíî ñ äèãîêñèíîì èíäóêòîðîâ Ð-ãëèêîïðîòåèíà (íàïðèìåð, ðèôàìïèöèíà), íàïðîòèâ, ïðèâîäèò ê ñíèæåíèþ óðîâíÿ äèãîêñèíà [5].

5
Li Y, Wang Y, Sun J, Li Y, Yang L. Distribution of the functionalMDR1 C3435T polymorphism in the Han population of China. Swiss Med Wkly. 2006; 136(23–24): 377–82.
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    Ñîâìåñòíîå ïðèìåíåíèå ñ äèãîêñèíîì ËÑ, èíãèáèðóþùèõ Ð-ãëèêîïðîòåèí, íàïðèìåð, êëàðèòðîìèöèíà, õèíèäèíà èëè öèêëîñïîðèíà, ïðèâîäèò ê çíà÷èòåëüíîìó ïîâûøåíèþ êîíöåíòðàöèè äèãîêñèíà â ïëàçìå êðîâè, à ïðèåì ñîâìåñòíî ñ äèãîêñèíîì èíäóêòîðîâ Ð-ãëèêîïðîòåèíà (íàïðèìåð, ðèôàìïèöèíà), íàïðîòèâ, ïðèâîäèò ê ñíèæåíèþ óðîâíÿ äèãîêñèíà
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    . Êðîìå òîãî, äèãîêñèí îïîñðåäîâàííî, ÷åðåç ðåöåïòîðû ñòåðîèäíûõ êñåíîáèîòèêîâ, óâåëè÷èâàåò óðîâåíü ýêñïðåññèè ãåíà Ð-ãëèêîïðîòåèíà [6].  2000 ã. áûëà îïóáëèêîâàíà ñòàòüÿ Hoffmeyer S. è ñîàâò., â êîòîðîé áûëè èçëîæåíû ðåçóëüòàòû ïåðâîãî èçó÷åíèÿ âçàèìîñâÿçè ïîëèìîðôèçìà ãåíàABCB1 ñ ôàðìàêîêèíåòèêîé äèãîêñèíà [7].

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Takara K, Takagi K, Tsujimoto M, Ohnishi N, Yokoyama T. Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and simultaneouslydown-regulatessteroidxenobioticreceptor mRNA. Biochem Biophys Res Commun. 2003; 306(1): 116–20.
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    íàïðèìåð, êëàðèòðîìèöèíà, õèíèäèíà èëè öèêëîñïîðèíà, ïðèâîäèò ê çíà÷èòåëüíîìó ïîâûøåíèþ êîíöåíòðàöèè äèãîêñèíà â ïëàçìå êðîâè, à ïðèåì ñîâìåñòíî ñ äèãîêñèíîì èíäóêòîðîâ Ð-ãëèêîïðîòåèíà (íàïðèìåð, ðèôàìïèöèíà), íàïðîòèâ, ïðèâîäèò ê ñíèæåíèþ óðîâíÿ äèãîêñèíà [5]. Êðîìå òîãî, äèãîêñèí îïîñðåäîâàííî, ÷åðåç ðåöåïòîðû ñòåðîèäíûõ êñåíîáèîòèêîâ, óâåëè÷èâàåò óðîâåíü ýêñïðåññèè ãåíà Ð-ãëèêîïðîòåèíà
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    .  2000 ã. áûëà îïóáëèêîâàíà ñòàòüÿ Hoffmeyer S. è ñîàâò., â êîòîðîé áûëè èçëîæåíû ðåçóëüòàòû ïåðâîãî èçó÷åíèÿ âçàèìîñâÿçè ïîëèìîðôèçìà ãåíàABCB1 ñ ôàðìàêîêèíåòèêîé äèãîêñèíà [7]. Ïðîàíàëèçèðîâàâ 15 ïîëèìîðôíûõ ìàðêåðîâ, àâòîðû îáíàðóæèëè, ÷òîÑmaxäèãîêñèíà ó ëèö ñ ãåíîòèïîì 3435ÒÒ â ïëàçìå êðîâè íà 38 % âûøå, ÷åì ó ëèö ñ ãåíîòèïîì 3435ÑÑ.

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Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000; 97(7): 3473–8.
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    Êðîìå òîãî, äèãîêñèí îïîñðåäîâàííî, ÷åðåç ðåöåïòîðû ñòåðîèäíûõ êñåíîáèîòèêîâ, óâåëè÷èâàåò óðîâåíü ýêñïðåññèè ãåíà Ð-ãëèêîïðîòåèíà [6].  2000 ã. áûëà îïóáëèêîâàíà ñòàòüÿ Hoffmeyer S. è ñîàâò., â êîòîðîé áûëè èçëîæåíû ðåçóëüòàòû ïåðâîãî èçó÷åíèÿ âçàèìîñâÿçè ïîëèìîðôèçìà ãåíàABCB1 ñ ôàðìàêîêèíåòèêîé äèãîêñèíà
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    . Ïðîàíàëèçèðîâàâ 15 ïîëèìîðôíûõ ìàðêåðîâ, àâòîðû îáíàðóæèëè, ÷òîÑmaxäèãîêñèíà ó ëèö ñ ãåíîòèïîì 3435ÒÒ â ïëàçìå êðîâè íà 38 % âûøå, ÷åì ó ëèö ñ ãåíîòèïîì 3435ÑÑ. Ïðè ýòîì ñîäåðæàíèå Ð-ãëèêîïðîòåèíà â äâåíàäöàòèïåðñòíîé êèøêå ó ëèö ñ ãåíîòèïîì 3435ÒÒ áûëî â 2 ðàçà ìåíüøå, ÷åì ó ãîìîçèãîò 3435ÑÑ.

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Chowbay B, Li H, David M, Cheung YB, Lee EJ. Meta-analysis of the influence ofMDR1C3435T polymorphism on digoxin pharmacokinetics and MDR1 gene expression. Br J Clin Pharmacol. 2005; 60(2): 159–71.
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    ïî ìíåíèþ àâòîðîâ îäíîãî èç ìåòà-àíàëèçîâ, íåñìîòðÿ íà äîñòîâåðíûå ðàçëè÷èÿ ïîêàçàòåëåéÑmaxèAUCïðè ïðèìåíåíèè äèãîêñèíà, íàëè÷èå àññîöèàöèè ïîëèìîðôèçìà Ñ3435Ò ñ ôàðìàêîêèíåòè÷åñêèìè ïîêàçàòåëÿìè è ýêñïðåññèåé P-ãëèêîïðîòåèíà ïîäòâåðæäåíî íå áûëî, è áûëî ïðåäëîæåíî â äàëüíåéøåì ñîñðåäîòî÷èòüñÿ íå íà àíàëèçå îäèíî÷íîãî ïîëèìîðôèçìà, à íà ó÷åòå èõ ñóììàðíîãî âëèÿíèÿ â ñîñòàâå ãàïëîòèïîâ
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    . Òåì íå ìåíåå, ñîãëàñíî ïðîâåäåííîìó â Ðîññèè èññëåäîâàíèþ, áûëî îáíàðóæåíî êàê íàðàñòàíèå óðîâíÿ äèãîêñèíà â ïëàçìå êðîâè â ðÿäó 3435ÑÑ – 3435ÑÒ – 3435ÒÒ, òàê è óâåëè÷åíèå â ýòîì ðÿäó ñèìïòîìîâ ãëèêîçèäíîé èíòîêñèêàöèè.

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Sychev DA, Ignatiev IV, Andreev DA, Poshukaeva LG, Kolkhir PV, Zhukova EE, et al. Glycoprotein P pharmacogenetic assessment role in digoxin pharmacotherapy individualization: a new approach for an old problem. Russian Journal of Cardiology 2006; (4): 64–8 (in Russian). al. The effect of 3435C>TMDR1gene polymorphism on rheumatoid arthritis treatment with disease-modifying antirheumatic drugs. Eur J Clin Pharmacol. 2006; 62(11): 933–7. 11. Drescher S, Schaeffeler E, Hitzl M, Hofmann U, Schwab M, Brinkmann U, et al.MDR1gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br J Clin Pharmacol. 2002; 53(5): 526–34. 12. Yi SY, Hong KS, Lim HS, Chung JY, Oh DS, Kim JR, et al. A variant 2677A allele of theMDR1gene affects fexofenadine disposition. Clin P
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    À. è ñîàâò. áûë ïðåäëîæåí àëãîðèòì äîçèðîâàíèÿ äèãîêñèíà, ñîãëàñíî êîòîðîìó ó ïàöèåíòîâ ñ ãåíîòèïîì 3435ÒÒ íåîáõîäèìî íà÷èíàòü ëå÷åíèå ñ ïîëîâèíû òåðàïåâòè÷åñêîé äîçû (1,125 ìã/ñóò) ïðè ìîíèòîðèíãå êîíöåíòðàöèè äèãîêñèíà â ïëàçìå êðîâè ïàöèåíòà âî èçáåæàíèå äèãèòàëèñíîé èíòîêñèêàöèè
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    . Ôåêñîôåíàäèí Ôåêñîôåíàäèí, àíòàãîíèñò Í1-ãèñòàìèíîâûõ ðåöåïòîðîâ III ïîêîëåíèÿ, íå îêàçûâàþùèé ñåäàòèâíîãî ýôôåêòà íà ÖÍÑ, èñïîëüçóåòñÿ â ìåäèöèíñêîé Òàáëèöà 2 ÑÏÈÑÎÊ ÍÀÈÁÎËÅÅ ÈÇÂÅÑÒÍÛÕ ËÅÊÀÐÑÒÂÅÍÍÛÕ ÑÐÅÄÑÒÂ,  ÂÛÂÅÄÅÍÈÈ ÊÎÒÎÐÛÕ ÈÇ ÎÐÃÀÍÈÇÌÀ Ó×ÀÑÒÂÓÅÒ Ð-ÃËÈÊÎÏÐÎÒÅÈÍ [15] Ãðóïïà ËÑÑóáñòðàòÐ-ãëèêîïðîòåèíà Äîïîëíèòåëüíîå âëèÿíèå íà Ð-ãëèêîïðîòåèí Ãðóïïà ËÑÑóáñòðàòÐ-ãëèêîïðîòåèíà Äîïîëíèòåëüíîå âëèÿ

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Drozdzik M, Rudas T, Pawlik A, Kurzawski M, Czerny B, Gornik W, et 23. McBride BF, Yang T, Roden DM. Influence of the G2677T/C3435T haplotype ofMDR1on P-glycoprotein trafficking and ibutilide-induced block of HERG. Pharmacogenomics J. 2009; 9(3): 194–201. 24. Sokova EA. Monitoring post-approvial drug safety in pregnancy:
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    Èçâåñòíî, ÷òî êåòîêîíàçîë ñ ýðèòðîìèöèíîì, èíãèáèðóþùèå P-ãëèêîïðîòåèí, âûçûâàþò ïðè ñîâìåñòíîì ïðèåìå óâåëè÷åíèå ñîäåðæàíèÿ ôåêñîôåíàäèíà â ïëàçìå êðîâè íà 64 è 9 % ñîîòâåòñòâåííî, à èíäóêòîð P-ãëèêîïðîòåèíà ðèôàìïèöèí âûçûâàåò îáðàòíûé ýôôåêò
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    . Ýòè íàáëþäåíèÿ ïîçâîëÿþò êîñâåííî îöåíèòü âêëàä Ð-ãëèêîïðîòåèíà â áèîäîñòóïíîñòü ôåêñîôåíàäèíà. Èçâåñòíî, ÷òî ôåêñîôåíàäèí ïðàêòè÷åñêè íå ïîäâåðãàåòñÿ áèîòðàíñôîðìàöèè, è ðîëü Ð-ãëèêîïðîòåèíà â åãî âûâåäåíèè ÿâëÿåòñÿ îñíîâîïîëàãàþùåé.