RESUMO
BEN is a primary, chronic tubulointerstitial nephritis characterized with chronic anemia, absence of edema, xantoderma, normal blood pressure and normal findings on the fundus oculi. The disease is distributed in restricted areas in Bulgaria, Romania, Croatia, Bosnia, Former Yugoslavia. Despite numerous studies on genetic and environmental factors and their possible involvement in BEN, its etiopathogenesis still remains elusive. Our recent study aim to elucidate the possible epigenetic component in BEN development. Whole genome DNA array methylation analysis was applied to compare the methylation profiles of male and female BEN patients from endemic regions in Bulgaria and Serbia and healthy controls. All three most prominent candidate genes with aberrations in the epigenetic profile discovered with this study are involved in the inflammatory/immune processes and oncogenesis. These data are in concordance with the reported pathological alterations in BEN. This research supports the role of epigenetic changes in BEN pathology. Exome sequencing of 22.000 genes with Illumina Nextera Exome Enrichment Kit revealed three mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients which encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.
Assuntos
Nefropatia dos Bálcãs/genética , Metilação de DNA , Epigênese Genética , Epigenômica , Genoma Humano , Genômica , Nefropatia dos Bálcãs/diagnóstico , Nefropatia dos Bálcãs/epidemiologia , Bulgária/epidemiologia , Estudos de Casos e Controles , Análise Mutacional de DNA , Epigenômica/métodos , Exoma , Feminino , Perfilação da Expressão Gênica , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Genômica/métodos , Proteoglicanas de Heparan Sulfato/genética , Humanos , Masculino , Mutação , Elastase Pancreática/genética , Fenótipo , Canais de Potássio de Domínios Poros em Tandem/genética , Fatores de Risco , Sérvia/epidemiologiaRESUMO
PAPP-A is one of the 2 biochemical markers of the first trimester Down syndrome serum screening. In Bulgaria this screening was first performed in 2006. The threshold values for evaluation of the risk of development of preeclampsia used by the researchers vary in a wide range. Nevertheless in the last several years the most used value is 0.4 MoM. The aim of represented study is evaluate the low PAPP-A levels as a marker for development of preeclampsia alone, or in combination with some risk factors. The data of 194 singleton pregnancies that underwent a first trimester Down syndrome screening between January 2008 and June 2009 had been analyzed. Twenty three patients (11.6%) developed preeclampsia, of which 8 required delivery before 34th gw. The control group includes 134 women who had term deliveries of healthy babies. Nine out of 23 (39%) patients with preeclampsia, 5 out of 8 (62.5%) patients with early onset preeclampsia and 42 out of 134 (30.4%) controls had PAPP-A levels below 0.4 MoM. These levels are associated with relative risk for development of preeclampsia of 1.5 times. Low PAPP-A levels in the first trimester were associated with a low prognostic value for development of preeclampsia and early preeclampsia before 34th gw. When low PAPP-A levels are added to the maternal age and especially results of Doppler evaluation of the uterine arteries significant prognostic value improvement was observed.
