Aberrant methylation in pediatric myelodysplastic syndrome
LEUKEMIA RESEARCH
Authors: Vidal, Daniel O.; Paixao, Valeria A.; Brait, Mariana; Souto, Elisabeth X.; Caballero, Otavia L.; Lopes, Luiz Fernando; Vettore, Andre L.
Abstract
Background: Aberrant methylation of gene promoter region is responsible for inappropriate gene silencing, and it has been associated to initiation and progression of cancer. Aberrant promoter methylation is frequently observed in adult patients with myelodysplastic syndrome (MDS), but in pediatric patients it has been poorly investigated. Methods: We examined the promoter methylation status of 13 genes in bone marrow cells collected at diagnosis of 21 pediatric patients with MDS (subtype RAEB or RAEB-t). For this analysis, we performed sodium bisulfite treatment of genomic DNA, followed by methylation specific PCR (MSP). Results: In pediatric MDS samples, we observed two genes frequently methylated: CALCA was methylated in 85.7% (18/21) of the analyzed samples and CDKN2B in 50% (6/12). Conclusions: Our findings indicate that CALCA and CDKN2B are frequently methylated in pediatric MDS. It suggests that aberrant methylation in pediatric MDS seems to be similar to adult MDS, thus pediatric patients could be also benefited with treatment using demethylating agents. (c) 2006 Elsevier Ltd. All fights reserved.
Association of CALCA genetic polymorphism with essential hypertension
CHINESE MEDICAL JOURNAL
Authors: Luo Xin-lin; Yang Tian-lun; Chen Xiao-ping; Li Yuan-jian
Abstract
Background Calcitonin gene-related peptide (CGRP) is the predominant neurotransmitter in capsaicin-sensitive sensory nerves. Participation of CGRP in hypertension is one of the most extensively studied topics in the field. There is growing evidence to the effect that CGRP is associated with essential hypertension (EH). The aims of this study were to pinpoint whether single nucleotide polymorphisms (SNPs) in the genes coding for CALCA were associated with EH susceptibility in a Hunan Han population. Methods A total of 293 subjects with EH and 208 controls were enrolled in the study. Genomic DNA was extracted from peripheral blood leucocytes by a phenol-chloroform method. The CALCA T-692C was genotyped using a restriction fragment length polymorphism method. Results A statistically significant difference in CALCA T-692C genotypic distribution was observed between cases and controls (P=0.001). Moreover, the frequencies of the C allele were 14.85% in the EH group and 7.45% in the control group, prevalence of C alleles in EH subjects and controls was significantly incomparable (P <0.001). Furthermore, the results of Logistic regression analysis showed that the carriers of C allele (TC+CC genotypes) were associated with increased EH risk (OR=2.093, 95% Cl: 1.317-3.326, P<0.01). Conclusions CALCA genetic polymorphism is associated with EH susceptibility. Carriers of at least one C allele at the polymorphic site CALCA T-692C showed increased risk for EH.