Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Quimioterapia de Consolidação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Melfalan/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/etiologia , Transplante de Células-Tronco/efeitos adversos , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
BACKGROUND: Pseudoxanthoma elasticum (PXE) is an inherited disorder of elastic tissue. We recently found that heterozygosity for the frequent (0.8% prevalence in Dutch population) R1141X mutation in the PXE gene coding for the ABCC6 transporter, is associated with a fourfold risk of premature coronary artery disease. Yet, it is not clear whether or not heterozygosity for this mutation results in a mild PXE phenotype. The objective of our study was to determine if skin and/or eye abnormalities related to a PXE phenotype could be found in patients with premature coronary artery disease, with and without the R1141X mutation. METHODS: R1141X mutation carriers with premature coronary artery disease (cases) and patients with premature coronary artery disease with no-or not known-mutation (controls) were studied. Cases and controls were examined for PXE-like skin changes and retinal angioid streaks, peau d'orange or pigment epithelium changes. RESULTS: 7 cases and 31 controls were analysed. In both the mutation-positive and the control group, skin inspection and eye fundus examination did not reveal any dermatological or ocular signs of PXE. CONCLUSIONS: Carriers for the ABCC6 R1141X mutation, which is frequent and confers a high risk of premature coronary artery disease, do not commonly have skin or eye abnormalities consistent with a mild PXE phenotype.
Assuntos
Doença das Coronárias/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Pseudoxantoma Elástico/genética , Adulto , Idade de Início , Comorbidade , Doença das Coronárias/epidemiologia , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fenótipo , Pseudoxantoma Elástico/epidemiologia , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Pseudoxanthoma elasticum (PXE) is an inborn disorder of the connective tissue with specific skin, ocular, and cardiovascular disease (CVD) manifestations. Recently, we and others have identified mutations in the gene coding for the ABCC6 transporter in PXE patients with ocular and skin involvement. In the Netherlands, as in the rest of Europe, a particular premature truncation variant ABCC6 (R1141X) was found in a large cohort of PXE patients. Given the association between CVD and PXE, we hypothesized that heterozygosity of this ABCC6 mutation could also confer an increased risk for CVD. METHODS AND RESULTS: To assess the relationship between the frequent R1141X mutation in the ABCC6 gene and the prevalence of premature coronary artery disease (CAD), we conducted a case-control study of 441 patients under the age of 50 years who had definite CAD and 1057 age- and sex-matched population-based controls who were free of coronary disease. Strikingly, the prevalence of the R1141X mutation was 4.2 times higher among patients than among controls (3.2% versus 0.8%; P<0.001). Consequently, among subjects with the R1141X mutation, the odds ratio for a coronary event was 4.23 (95% CI: 1.76 to 10.20, P= 0.001). CONCLUSION: The presence of the R1141X mutation in the ABCC6 gene is associated with a sharply increased risk of premature CAD.