RESUMEN
BACKGROUND: Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease in immunocompromised patients including allograft recipients. Detection of KSHV DNA in blood, as well as host genetic polymorphisms has been found to be associated with an increased risk for KS. We investigated an association between single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA) gene region and KSHV viremia in kidney transplant recipients (KTR) in Saudi Arabia. METHODS: In total, 152 KTR who have survived kidney transplantation for at least 6 months were included in the study. KSHV viremia was determined by real-time polymerase chain reaction (PCR). Genotyping of SNPs in the VEGFA region was performed by PCR and direct sequencing, as well as by restriction fragment length polymorphism. RESULTS: KSHV DNA was detected in 28.9% (n = 44) of the study population. The A-allele at position C172A VEGFA gene promoter region was found to be associated with KSHV viremia (odd ratio [OR] = 4.8, P = 0.005). In addition, the G-allele at position C+405G in the 5'-untranslated region was associated with KSHV viremia in women, but not in men (OR = 3.98, P = 0.004). CONCLUSIONS: Our results suggest an association of VEGFA polymorphisms with KSHV viremia among KTR in this study population. A limitation of our study is that the results can only be predicated for patients 6 months after kidney transplantation and should be validated in another cohort with larger sample size.
Asunto(s)
Infecciones por Herpesviridae/genética , Herpesvirus Humano 8/aislamiento & purificación , Huésped Inmunocomprometido/genética , Trasplante de Riñón/efectos adversos , Factor A de Crecimiento Endotelial Vascular/genética , Viremia/genética , Regiones no Traducidas 5' , Adulto , Aloinjertos , Femenino , Genotipo , Infecciones por Herpesviridae/virología , Humanos , Masculino , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Arabia Saudita , Factores Sexuales , Viremia/inmunología , Viremia/virologíaRESUMEN
Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria (DSH) are pigmentary dermatoses most commonly seen in Japan. Both disorders usually show autosomal dominant inheritance, although in some cases autosomal recessive inheritance was reported. DSH was mapped to chromosome 1q21.3, and mutations in the gene ADAR (DSRAD) were identified in Japanese, Chinese and Taiwanese families with autosomal dominant DSH. A second locus for dyschromatosis was mapped on chromosome 6q24.2-q25.2 in two Chinese families initially reported to be affected with DSH, but later suggested to have autosomal dominant DUH. The aim of this study was to investigate whether one of these two loci is involved in the development of DUH in a consanguineous Bedouin family from Saudi Arabia with four affected and three unaffected sibs, clearly pointing to autosomal recessive inheritance. After excluding mutations in ADAR and linkage to the candidate regions on chromosomes 1 and 6, we performed an single nucleotide polymorphism-based genome-wide scan for linkage with other loci. Under the assumption of autosomal recessive inheritance, we have identified a new locus for dyschromatosis on chromosome 12q21-q23 in this Arab family with a maximum logarithm of the odds (LOD) score of 3.4, spanning a distance of 18.9 cM. Our study revealed the first locus for autosomal recessive DUH and supports recent evidence that DSH and DUH are genetically distinct disorders.