Pesquisadores do Precision Healthcare Research Institute (PHURI) da Queen Mary University of London e do Berlin Institute of Health (BIH) da Charité—Universitätsmedizin Berlin identificaram as causas genéticas do fenômeno de Raynaud.
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)
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Pesquisadores do Precision Healthcare Research Institute (PHURI) da Queen Mary University of London e do Berlin Institute of Health (BIH) da Charité—Universitätsmedizin Berlin identificaram as causas genéticas do fenômeno de Raynaud. Suas descobertas, publicadas hoje na Nature Communications , podem levar aos primeiros tratamentos eficazes para pessoas com Raynaud.
O fenômeno de Raynaud (PR) é uma condição hereditária que afeta a circulação sanguínea . É uma condição vasopástica, o que significa que pequenos vasos sanguíneos próximos à superfície da pele apresentam espasmos que podem limitar o fluxo sanguíneo . As pessoas com Raynaud geralmente sentem dor nos dedos das mãos e dos pés, muitas vezes ao lado de mudanças na cor da pele, devido à falta de fluxo sanguíneo durante os ataques quando estão com frio ou emocionalmente estressados. Em casos mais graves, pode causar dores intensas ou úlceras.
Cerca de 2-5% da população são afetados por Raynaud. Apesar de ser uma condição comum, é pouco investigada e pouco se sabe sobre a causa genética da doença.
Existem tratamentos limitados disponíveis para RP. Os médicos geralmente aconselham que o paciente use estratégias de "autocontrole", como manter-se aquecido e evitar os gatilhos dos ataques. Em casos graves podem ser prescritos medicamentos; estes são "medicamentos reaproveitados", geralmente medicamentos para baixar a pressão arterial elevada. Estes geralmente causam efeitos colaterais graves em pacientes. É necessária uma melhor compreensão dos mecanismos genéticos subjacentes que causam DR para desenvolver tratamentos seguros e eficazes.
Pesquisadores liderados pela professora Claudia Langenberg e pelo professor Maik Pietzner, trabalhando no PHURI e no BIH, realizaram o maior estudo de associação do genoma (GWAS) para o fenômeno de Raynaud. A equipe usou registros eletrônicos de saúde do UK Biobank, um banco de dados biomédico em larga escala e recurso de pesquisa contendo informações genéticas e de saúde de meio milhão de participantes do Reino Unido, para identificar mais de 9.000 pessoas afetadas pela doença de Raynaud. A equipe também usou registros eletrônicos de saúde do estudo Queen Mary's Genes & Health.
As evidências
Os pesquisadores descobriram variações em dois genes que predispunham os participantes ao fenômeno de Raynaud: um era o receptor alfa-2A- adrenérgico para adrenalina, ADRA2A, um receptor de estresse clássico que causa a contração dos pequenos vasos sanguíneos.
"Isso faz sentido quando está frio ou perigoso, porque o corpo precisa fornecer sangue ao interior do corpo", explica Maik Pietzner, presidente de dados de saúde do PHURI e colíder do Grupo de Medicina Computacional do BIH.
"Nos pacientes de Raynaud, no entanto, esse receptor parecia estar particularmente ativo, o que poderia explicar os vasoespasmos, especialmente em combinação com o segundo gene que encontramos: esse gene é o fator de transcrição IRX1, que pode regular a capacidade dos vasos sanguíneos de dilatar .
"Se sua produção for aumentada, pode ativar genes que impedem que os vasos constritos relaxem como fariam normalmente. Junto com o receptor hiperativo de adrenalina, isso pode fazer com que os vasos não forneçam sangue suficiente por um longo período de tempo, o que leva aos dedos das mãos e pés brancos observados."
Os pesquisadores também foram capazes de replicar partes de suas descobertas usando dados de participantes de origem britânica de Bangladesh e Paquistão do estudo Queen Mary's Genes & Health.
As descobertas dos pesquisadores também ajudam a entender pela primeira vez por que os pequenos vasos reagem tão fortemente nos pacientes, mesmo aparentemente sem estímulos externos, como a exposição ao frio.
A Dra. Emma Blamont, chefe de pesquisa para esclerodermia e Reino Unido de Raynaud (SRUK), disse: "A doença de Raynaud é uma condição dolorosa e crônica que afeta cerca de uma em cada dez pessoas no Reino Unido. Sabemos que os ataques podem ser causados ??por certos gatilhos, como frio e estresse, mas relativamente pouco se sabe sobre por que algumas pessoas sofrem de Raynaud e outras não. Para milhões de pessoas que vivem com essa condição, tarefas simples do dia a dia podem ser um desafio, então pesquisas como esta, que avançam significativamente nossa compreensão Raynaud e o papel que a genética pode desempenhar em sua causa são cruciais.
"O próximo passo é confirmar essas descobertas importantes em grupos populacionais mais diversos e validar os resultados por meio de estudos funcionais. Se forem bem-sucedidas, essas descobertas podem nos ajudar a desvendar novos caminhos terapêuticos para o Raynaud, levando a tratamentos melhores, mais direcionados e mais gentis".
As descobertas podem levar a recomendações para os pacientes para ajudar a controlar a condição. Por exemplo, os pesquisadores mostraram que pessoas com predisposição genética a níveis baixos de açúcar no sangue têm um risco aumentado de fenômeno de Raynaud e, portanto, os pacientes devem evitar episódios mais longos de baixo nível de açúcar no sangue. Suas descobertas podem até apontar para novas opções de tratamento, como Claudia Langenberg explicou: "Por exemplo, drogas já aprovadas que inibem mais ou menos especificamente a função de ADRA2A podem ser uma alternativa, como o antidepressivo mirtazapina. Estou convencida de que nossas descobertas fornecem um caminho para novos medicamentos eficazes."
Mais informações: Sylvia Hartmann, Maik Pietzner, Claudia Langenberg, ADRA2A e IRX1 são genes de risco putativos para o fenômeno de Raynaud, Nature Communications (2023). DOI: 10.1038/s41467-023-40200-5
Informações do jornal: Nature Communications