Ó÷èòûâàÿ ôàêò ãåíåòè÷åñêîé ãåòåðîãåííîñòè ãèïåðëèïèäåìèé, ïîëèìîðôíûå âàðèàíòû ãå-íîâ, âîâëå÷åííûõ â ðåãóëÿöèþ ëèïèäíîãî îáìåíà, ìîãóò îïðåäåëÿòü ðàçëè÷èÿ â ýôôåêòèâíîñòè ïðèìåíÿåìûõ ó ïàöèåíòîâ ãèïîëèïèäåìè÷åñêèõ ïðåïàðàòîâ.  ðàìêàõ íàñòîÿùåãî ïðîñòîãî, ïðîñïåêòèâíîãî, ðàíäîìèçèðîâàííîãî èññëåäîâàíèÿ èçó÷åíà ýôôåêòèâíîñòü ïðèìåíåíèÿ ðîçóâà-ñòàòèíà â äîçå 10 ìã/ñóòêè äëÿ ëå÷åíèÿ àòåðîãåííûõ ãèïåðëèïèäåìèé ó 62 ïàöèåíòîâ ñ èøåìè÷å-ñêîé áîëåçíüþ ñåðäöà (ÈÁÑ) â çàâèñèìîñòè îò ãåíîòèïîâ ëèïîïðîòåèíëèïàçû (LPL). Ôàðìàêîëî-ãè÷åñêàÿ êîððåêöèÿ ïðîâîäèëàñü â òå÷åíèå ãîäà ñ êîíòðîëåì ïàðàìåòðîâ ëèïèäíîãî îáìåíà (ÎÕÑ, ÕÑ ËÍÏ, ÕÑ ËÂÏ, ÕÑ, íå ñâÿçàííûé ñ ËÂÏ, òðèãëèöåðèäû, àòåðîãåííûé èíäåêñ) â ìî-ìåíò âêëþ÷åíèÿ, ÷åðåç 4, 8, 24 è 48 íåäåëü. Ó âñåõ ïàöèåíòîâ ïðîâåäåíî ãåíîòèïèðîâàíèå ïîëè-ìîðôèçìà Hind III (+495T>G, rs320) ãåíà LPL ìåòîäîì ÏÖÐ â ðåaeèìå ðåàëüíîãî âðåìåíè ñ èñïî-ëüçîâàíèåì TaqMan-çîíäîâ äëÿ äèñêðèìèíàöèè àëëåëåé. Ðîçóâàñòàòèí ïîêàçàë çíà÷èòåëüíûé ãè-ïîëèïèäåìè÷åñêèé ýôôåêò â îòíîøåíèè âñåõ èññëåäîâàííûõ ïîêàçàòåëåé ëèïèäíîãî îáìåíà óaeå íà 24 íåäåëå ëå÷åíèÿ. Äèíàìèêà èçìåíåíèé ïîêàçàòåëåé ëèïèäíîãî îáìåíà íà ôîíå ëå÷åíèÿ îò-ëè÷àëàñü ó ïàöèåíòîâ ñ ãåíîòèïîì +495GG â ñðàâíåíèè ñ äðóãèìè ãåíîòèïàìè LPL.  ñðàâíåíèè ñ ãåíîòèïàìè +495TT è TG, íîñèòåëè ãåíîòèïà +495GG èìåëè áîëåå âûðàaeåííîå ñíèaeåíèå îá-ùåãî õîëåñòåðèíà íà 8 íåäåëå, ÕÑ ËÍÏ è ÕÑ íåñâÿçàííîãî ñ ËÂÏ, à òàêaeå àòåðîãåííîãî èíäåêñà íà 48 íåäåëå òåðàïèè ðîçóâàñòàòèíîì (p < 0,01). Ïî âñåé âèäèìîñòè, áîëåå âûðàaeåííûé ãèïîëè-ïèäåìè÷åñêèé ýôôåêò ðîçóâàñòàòèíà ó ãîìîçèãîò +495GG ãåíà LPL ñâÿçàí ñ ìîäóëÿöèåé àêòèâ-íîñòè ôåðìåíòà, êàê ýòî áûëî ðàíåå îáíàðóaeåíî ó äðóãèõ ñòàòèíîâûõ ïðåïàðàòîâ.Êëþ÷åâûå ñëîâà: ãèïîëèïèäåìè÷åñêàÿ òåðàïèÿ; ðîçóâàñòàòèí; ëèïîïðîòåèíëèïàçà; ÄÍÊ-ïîëèìîðôèçì; ôàðìàêîãåíåòèêà. ÂÂÅÄÅÍÈÅ èíäóñòðèàëüíûõ ñòðàíàõ èøåìè÷åñêàÿ áîëåçíü ñåðäöà (ÈÁÑ) -ñàìàÿ ÷àñòàÿ ïðè÷èíà ëåòàëüíîñòè è ïîòåðè òðóäîñïîñîáíîñòè ïî áîëåçíè [2,5]. Îñíîâíîé ïðè÷èíîé ÈÁÑ ÿâëÿåòñÿ àòåðîñêëåðîç êîðîíàðíûõ àð-òåðèé, âîçíèêàþùèé â ðåçóëüòàòå íàðóøåíèÿ îáìåíà ëèïèäîâ. Ãåíû, âîâëå÷åííûå â ðåãóëÿöèþ ëèïèäíîãî îáìåíà (ËÎ), ðàññìàòðèâàþòñÿ êàê çíà÷èìûå ãåíåòè-÷åñêèå ôàêòîðû ðèñêà ÈÁÑ [7,11]. Ñðåäè âîçìîaeíûõ ãåíîâ-êàíäèäàòîâ ïîäâåðaeåííîñòè ÈÁÑ âûäåëÿþò ãåí ëèïîïðîòåèíëèïàçû (LPL ) -ôåðìåíò, îáåñïå÷èâàþ-ùèé ãèäðîëèç òðèãëèöåðèäîâ (ÒÃ) è ïðåâðàùåíèå õî-ëåñòåðèíà ëèïîïðîòåèäîâ î÷åíü íèçêîé ïëîòíîñòè (ÕÑ ËÎÍÏ) â õîëåñòåðèí ëèïîïðîòåèäîâ íèçêîé ïëîò-íîñòè (ÕÑ ËÍÏ) [4,5]. Ïîëèìîðôèçìû ãåíà LPL îïðå-äåëÿþò ôóíêöèîíàëüíóþ àêòèâíîñòü ôåðìåíòà è, òà-êèì îáðàçîì, ìîãóò âíîñèòü âêëàä â ïðåäðàñïîëîaeåí-íîñòü íîñèòåëåé ê ãèïåðëèïèäåìèè (ÃËÏ). Îäíèì èç ÷àñòûõ ïîëèìîðôèçìîâ ãåíà LPL ÿâëÿåòñÿ çàìåíà ãóà-íèíà (G) íà òèìèí (T) â ïîëîaeåíèè + 495 èíòðîíà 8, èçìåíÿþùàÿ ñàéò óçíàâàíèÿ ðåñòðèêòàçîé Hind III, òàê íàçûâàåìûé Hind III-ïîëèìîðôèçì [3], âëèÿþùèé íà àêòèâíîñòü ôåðìåíòà [7,13]. Äàííûé ïîëèìîðôèçì àññîöèèðóåòñÿ ñ ïîíèaeåííûì ðèñêîì ðàçâèòèÿ ÈÁÑ, êàê ýòî áûëî íåîäíîêðàòíî îáíàðóaeåíî â ðåòðîñïåê-òèâíûõ èññëåäîâàíèÿõ [3,12,13]. Îäíàêî âëèÿíèå ãå-íîòèïà íà ýôôåêòèâíîñòü ãèïîëèïèäåìè÷åñêîé òå...
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