Disease Progression, Response to ACEI/ATRA Therapy and Influence of ACE Gene in IgA Nephritis

Various studies have shown that angiotensin-converting enzyme （ACE） gene insertion/deletion （ID） polymorphism may play a role in the progression to end stage renal failure （ESRF） in patients with IgA nephritis （IgAN）. In this randomized controlled trial, patients were followed up for 5 years to determine their long-term renal outcome to ACEI/ATRA therapy and to ascertain if their ACE gene profile could play a role in determining their response to therapy. Seventy-five patients with IgAN were enlisted. Thirty-seven were on ACEI/ATRA therapy for 62 ± 5 months and thirty-eight were untreated and served as controls. All patients had their ACE gene ID polymorphism genotyped. Compared to controls, treated patients had lower serum creatinine （p 〈 0.001）, lower proteinuria （p 〈 0.002） and fewer numbers progressing to ESRF （p 〈 0.002）. Among patients with genotype II, there were less ESRF in the treatment group when compared to the untreated control group （p 〈 0.02）. The advantage of therapy was not seen in patients with ID or DD genotypes. ACEI/ATRA therapy was found to be effective in retarding disease progression in IgAN with years to ESRF significantly extended in patients at all levels of renal function, including patients whose outcome were ESRF. Genotyping showed better response to therapy only for those with genotype Ⅱ. The common mechanism is probably through lower levels of ACE, glomerular pressure and proteinuria resulting in reduced renal damage and retardation of progression to ESRF. Cellular ＆ Molecular Immunology.

Quantitative Detection of ID4 Gene Aberrant Methylation in the Differentiation of Myelodysplastic Syndrome from Aplastic Anemia

Background：The diagnosis of myelodysplastic syndrome （MDS）,especially hypoplastic MDS,and MDS with low blast counts or normal karyotype may be problematic.This study characterized ID4 gene methylation in patients with MDS and aplastic anemia （AA）.Methods：The methylation status ofID4 was analyzed by bisulfite sequencing polymerase chain reaction （PCR） and quantitative real-time methylation-specific PCR （MethyLight PCR） in 100 patients with MDS and 31 patients with AA.Results：The MDS group had a higher ID4 gene methylation positivity rate （22.22%） and higher methylation levels （0.21 [0-3.79]） than the AA group （P 〈 0.05）.Furthermore,there were significant differences between the hypoplastic MDS and AA groups,the MDS with low blast count and the AA groups,and the MDS with normal karyotype and the AA groups.The combination of genetic and epigenetic markers was used in much more patients with MDS （62.5% [35/56]） than the use of genetic markers only （51.79% [29/56]）.Conclusions：These results showed that the detection ofID4 methylation positivity rates and levels could be a useful biomarker for MDS diagnosis.