Гены-кандидаты развития антипсихотик-индуцированного паркинсонизма у пациентов с шизофренией

Антипсихотик-индуцированный паркинсонизм—нежелательная реакция со стороны экстрапирамидной системы, возникающая на фоне приема антипсихотиков (АП), чаще у пациентов с шизофренией. АП-индуцированный паркинсонизм (АИП) относится к группе вторичного паркинсонизма. Его распространенность в мире составляет около 36%. Предполагается, что эта нежелательная реакция (НР) генетически детерминирована. В последние годы проведены многочисленные ассоциативные генетические исследования предрасположенности к развитию АИП. Однако, результаты исследований противоречивы.
Цель. Обзор результатов исследований генетических предикторов развития антипсихотик-индуцированного паркинсонизма у пациентов с шизофренией.
Материалы и методы. Нами проведен поиск полнотекстовых публикаций на русском и английском языках в базах данных РИНЦ, PubMed, Web of Science, Springer, используя ключевые слова и комбинированные поиски слов за последнее 10-летие.
Результаты. В обзоре рассмотрены гены-кандидаты, кодирующие белки/ферменты, участвующие в фармакодинамике и фармакокинетике АП. Нами проанализировано 23 ассоциативных генетических исследования, изучающих 108 генетических вариаций, включая ОНВ/полиморфизмы 26 геновкандидатов, участвующих в развитии АИП у пациентов с шизофренией. Среди такого множества полученных результатов выявлено всего 22 положительные ассоциации: rs1799732 (141CIns / Del), rs1800497 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3; VNTR*9R DAT1; rs4680 (G/A) СOMT; rs6311 (C/T) 5HTR2A; rs6318 (C/G), rs3813929 (С/Т), гаплотип -997G, -759C, -697C и 68G HTR2C; rs2179652 (C/T), rs2746073 (T/A), rs4606 (C/G), rs1152746 (A/G), rs1819741 (С/Т), rs1933695 (G/A), гаплотип rs1933695-G, rs2179652-C, rs4606-C, rs1819741-T и rs1152746-G, гаплотип rs1933695-G, rs2179652-T, rs4606-G, rs1819741-C и rs1152746-A RGS2; Гаплотип TCCTC ADORA2A; rs4795390 (C/G) PPP1R1B; rs6265 (G/A) BDNF; rs12678719 (C/G) ZFPM2; rs938112 (C/A) LSMAP; rs2987902 (A/T) ABL1; HLA-B44; rs16947 (A/G), rs1135824 (A/G), rs3892097 (A/G), rs28371733 (A/G), rs5030867 (A/C), rs5030865 (A/C), rs1065852 (C/T), rs5030863 (C/G), rs5030862 (A/G), rs28371706 (C/T), rs28371725 (A/G), rs1080983 (A/G) CYP2D6. Однако, в настоящее время следует признать, что нет окончательного или единственного решения о ведущей роли какого-либо конкретного ОНВ/полиморфизма в развитии АИП.
Заключение. Раскрытие генетических предикторов развития АИП, как наиболее распространенной неврологической НР при лечении пациентов с психиатрическими расстройствами, может дать ключ к разработке стратегии персонализированной профилактики и терапии рассматриваемого осложнения АП-терапии шизофрении в реальной клинической практике.

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