RESUMO
Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of â¼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of â¼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.
Assuntos
Predisposição Genética para Doença , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Hispânico ou Latino/genética , Fator de Transcrição Ikaros/genéticaRESUMO
There are a variety of cardiac complications of anorexia nervosa including arrythmias, valvopathies, and myopathies. Spontaneous coronary artery dissection (SCAD) has not been widely reported among this patient population. This case report describes a middle-aged female with severe anorexia nervosa, who presented after being found unconscious, and was later diagnosed with SCAD. A literature review revealed one previous case of SCAD in a patient with anorexia nervosa and prompted a discussion of a series of possible predisposing factors for SCAD in this patient population. Patients with anorexia nervosa may be at increased risk for SCAD due to their complex nutritional and endocrine imbalances. This case highlights a possible underdiagnosed cardiac complication of anorexia nervosa.