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Мутации в генах лептина и его медиаторов: индукция ожирения в сочетании с разной патологией

https://doi.org/10.14341/probl201359249-59

Аннотация

В гомозиготном состоянии мутации g.15384delG(G133fsX15), c.215T⇒C(p.L72S), c.309C⇒A(p.N103K), c.313C⇒T(p.R105W), c.422C⇒G(p.S141C), c.104_106delTCA, c.481_482delCT и c.135del3bp в LEP ассоциированы с ранним началом тяжелого ожирения и нарушением многих физиологических функций. Аналогичную патологию индуцируют мутации в LEPR: замена G⇒A в донорном сайте сплайсинга; делеции 4 и 11 п.о. в 5´-конце сДНК; делеция 66 п.о. в CRH домене LEPR; компаунд делеция 1 п.о. в 5´-конце/p.R612H и миссенс-мутации - P316T, A409E, W664R, H684P. Нарушения экспрессии LEP и LEPR сочетаются у гомозигот с тяжелым ожирением, задержкой полового развития, резистентностью к инсулину, изменением секреции гормонов аденогипофиза и иммунодефицитом. Мутации в LEP вызывают более тяжелую патологию, чем мутации в LEPR. В гомозиготном состоянии мутации в POMC: 3804C⇒A, 6906delC, 6922insC и компаунд гетерозиготные мутации 7134delG/7013G⇒T, 6996del/6851A⇒T, 3804C⇒A/7100insGG ассоциированы у человека с морбидным ожирением и острой недостаточностью коры надпочечников. В гетерозиготном состоянии они предрасполагают к ожирению без других нарушений. Мутации в MC4R являются наиболее распространенной причиной ожирения. Они индуцируют тяжелую патологию у гомозигот, но ассоциированы с более легкими нарушениями жирового обмена у гетерозигот. В обоих случаях ожирение не сопровождается серьезными нарушениями других функций.

Об авторе

Iu Pankov



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Для цитирования:


. Мутации в генах лептина и его медиаторов: индукция ожирения в сочетании с разной патологией. Проблемы Эндокринологии. 2013;59(2):49-59. https://doi.org/10.14341/probl201359249-59

For citation:


Pankov I.A. Mutations in the genes encoding for leptin and its mediators: induction of obesity with various concomitant pathological conditions. Problems of Endocrinology. 2013;59(2):49-59. (In Russ.) https://doi.org/10.14341/probl201359249-59

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