External suppression causes the low expression of the Cosmc gene in IgA nephropathy

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Wei QinXing Yi Ma

Abstract

IgA(1) aberrant O-glycosylation is one of the main pathogeneses of IgA nephropathy (IgAN), and the core I beta3-Gal-T-specific molecular chaperone (Cosmc) mRNA expression of IgAN patients was significantly decreased. This study tried to clarify whether the down-regulation was a result of genetic disorders or external suppressions. Sixty-five IgAN patients, 23 non-IgAN glomerulonephritis patients and 21 normal controls were recruited. Genomic DNA was extracted and the Cosmc gene was PCR amplified and directly sequenced. Peripheral B lymphocytes of IgAN patients and normal controls were isolated, and cultured with RPMI-1640 alone or with lipopolysaccharide (LPS) for 72 h. The Cosmc mRNA expression levels at baseline, after RPMI culture or RPMI + LPS treatment were measured by real-time RT-PCR. (1) The whole coding frame region of the Cosmc gene was successfully amplified and directly sequenced. Four single nucleotide polymorphisms were detected in two IgAN patients. Two were missense mutations and the others were silent mutations. However, they are different from each other, and unrelated to expression levels; (2) the baseline Cosmc mRNA expression in IgAN patients was significantly lower than normal controls (Ct(COSMC/GAPDH) 1.2...Continue Reading

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