RESUMO
Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Doença de Alzheimer/etnologia , Doença de Alzheimer/genética , Glicoproteínas de Membrana/genética , Fosfolipase C gama/genética , Receptores Imunológicos/genética , Idoso , Idoso de 80 Anos ou mais , Argentina/etnologia , População Negra/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Indígenas Norte-Americanos/genética , Masculino , Pessoa de Meia-Idade , População Branca/genéticaRESUMO
Background: Diabetic foot ulcer is one of the frequent complications of diabetes. 15% to 25% develop ulcers at some point in their lives. The existing evidence on the efficacy of topical autologous platelet-rich plasma (PRP) for the treatment of diabetic foot ulcers was assessed. Method: A search for randomized controlled clinical trials comparing autologous topical PRP vs standard care and placebo was carried out in Pubmed, Cochrane, Lilacs, and Clinical Trials databases. For dichotomous outcomes, relative risk analysis, 95% CI, and the Mantel-Haenszel method were used; for continuous outcomes, the mean difference and inverse variance method were calculated. Results: The result of the search was 153 studies, 28 duplicates were excluded, 59 by title and abstract, and 52 by reading the article. 14 studies were included in the review, 8 for qualitative review and 6 for quantitative. Six studies with a complete ulcer-healing outcome at the end of the intervention were evaluated, out of a total of 415 participants (relative risk 1.24 CI [1.11, 1.40]). The outcome epithelialized area at the end of the intervention, measured in cm², was not reported. A single study measured quality of life and pain. Conclusion: There is evidence of the beneficial effect of topical autologous PRP for the healing of diabetic foot ulcers, however, studies of higher methodological quality, greater production of clinical trials in Latin America, and assessment of the quality of life and pain are needed.
Antecedentes: La úlcera de pie diabético constituye una de las complicaciones frecuentes de la diabetes. Del 15% al 25% de los pacientes presentan úlceras en algún momento de su vida. Se valoró la evidencia existente sobre la eficacia del plasma rico en plaquetas (PRP) autólogo tópico para el tratamiento de úlcera de pie diabético. Método: Se llevó a cabo a partir de datos de Pubmed, Cochrane, Lilacs y Clinical Trials, búsqueda de ensayos clínicos aleatorizados controlados que compararon PRP autólogo tópico frente a cuidados estándar y placebo. Para los resultados dicotómicos se usó el análisis de riesgo relativo, con intervalos de confianza del 95% y el método de Mantel-Haenszel; para los resultados continuos, se calculó la diferencia de medias y método de varianza inversa. Resultados: El resultado de la búsqueda fue 153 estudios, se excluyeron 28 duplicados, 59 por título y abstract y 52 por lectura de artículo. Se incluyeron 14 trabajos en la revisión, 8 para revisión cualitativa y 6 para cuantitativa. Se valoraron 6 estudios con desenlace de curación completa de úlcera al final de la intervención, sobre un total de 415 participantes (riesgo relativo 1.24 [IC 95%: 1.11 a 1.40]). No se informó el desenlace área epitelizada al final de la intervención medida en cm². Un solo estudio midió calidad de vida y dolor. Conclusión: Existe evidencia del efecto beneficioso del PRP autólogo tópico para la curación de úlcera de pie diabético; no obstante, se necesitan estudios de mayor calidad metodológica, mayor producción de ensayos clínicos en Latinoamérica y valoración de calidad de vida y dolor.