Dataset Information

Changes to signal peptide and the level of transforming growth factor- ?1 due to T869C polymorphism of TGF ?1 associated with lupus renal fibrosis.

ABSTRACT: Lupus Nephritis (LN) is a serious manifestation of lupus that can lead to End Stage Renal Disease (ESRD). Fibrosis is the main feature of ESRD, and it is likely influenced by Transforming Growth Factor Beta1 (TGF?1). The T869C gene polymorphism of TGF?1 is assumed to change the signal peptide, that has potential to interfere the urine production and renal protein expression of TGF?1. The influence of T869C gene polymorphism on TGF?1 production and renal fibrosis was evaluated in this study. Subjects were 45 patients LN with renal fibrosis and 45 participants without renal fibrosis as control, that were recruited from 2011 to 2013.Their urinary TGF?1 levels and TGF?1 gene polymorphisms were examined. All lupus patients underwent renal biopsy to assess their protein expression of TGF?1 in the renal tissue by immunohistochemistry and their renal fibrosis by morphometry and chronicity index. Changes in the signal peptide interaction with Signal Recognition Particle (SRP) and translocon of endoplasmic reticulum were analyzed by Bioinformatics. Levels of urinary and protein expression of TGF?1 increased in the LN with renal fibrosis group. There were significant differences in levels of urinary TGF?1 in T, C allele and TT, TC, CC genotypes between case and control groups. Furthermore, patients with C allele are 3.86 times more at risk of renal fibrosis than T allele. The C allele encodes proline, which stabilizes the interaction of the TGF?1 signal peptide with SRP and translocon, resulting in elevation of TGF?1 secretion. Our results indicated that T869C gene polymorphism of TGF?1 changes the signal peptide, that contributes to the production of urinary TGF?1 and affects renal fibrosis in lupus nephritis.

SUBMITTER: Susianti H

PROVIDER: S-EPMC4179638 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Changes to signal peptide and the level of transforming growth factor- β1 due to T869C polymorphism of TGF β1 associated with lupus renal fibrosis.

Susianti Hani H Handono Kusworini K Purnomo Basuki B BB Widodo Nashi N Gunawan Atma A Kalim Handono H

SpringerPlus 20140910

Lupus Nephritis (LN) is a serious manifestation of lupus that can lead to End Stage Renal Disease (ESRD). Fibrosis is the main feature of ESRD, and it is likely influenced by Transforming Growth Factor Beta1 (TGFβ1). The T869C gene polymorphism of TGFβ1 is assumed to change the signal peptide, that has potential to interfere the urine production and renal protein expression of TGFβ1. The influence of T869C gene polymorphism on TGFβ1 production and renal fibrosis was evaluated in this study. Subj ...[more]

PMID: 25279306

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Project description:ObjectiveTo explore the association between transforming growth factor-beta1 (TGF-?1) T869C polymorphism and risk of ischemic stroke (IS) by performing a meta-analysis based on published articles.MethodsSystematic electronic searches of PubMed, Science Direct, BIOSIS Previews, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and WANFANG Database were performed. The strength of the association was calculated by pooled odds ratios (ORs) with 95% confidence intervals (95%CIs). Subgroup analysis was conducted to explore potential sources of heterogeneity. Sensitivity analysis was performed to elucidate the stability of the outcomes. Publication bias was evaluated by Begg's funnel plot and Egger's test.ResultsA total of 6 studies involving 1701 cases were included. The overall estimates did not show any significant association between TGF-?1 T869C polymorphism and risk of IS under all genetic models (C vs. T: OR?=?1.08,95%CI?=?0.88-1.32; CC vs. TT:OR?=?1.17,95%CI?=?0.79-1.72; CT vs. TT: OR?=?0.91, 95%CI?=?0.68-1.22; CC+CT vs. TT: OR?=?0.99, 95%CI?=?0.73-1.35; CC vs. CT+TT: OR?=?1.23, 95%CI?=?0.95-1.59). Similar lacking associations were observed in subgroup analysis based on ethnicity and source of controls. When stratified by study design, significant increased association of IS risk was found in cohort studies under genetic models except recessive model(C vs. T: OR?=?1.18, 95%CI?=?1.05-1.32; CC vs. TT: OR?=?1.40, 95%CI?=?1.10-1.77; CT vs. TT: OR?=?1.23, 95%CI?=?1.02-1.49; CC+CT vs. TT: OR?=?1.27, 95%CI?=?1.03-1.57; CC vs. CT+TT, OR?=?1.21, 95%CI?=?0.99-1.47), whereas in case-control studies a significant decreased risk was detected under heterozygote comparison(CT vs. CC: OR?=?0.72, 95%CI?=?0.57-0.92). However, after correction for multiple testing, the associations were observed to be null significant in both cohort and case-control subgroups among all genetic models.ConclusionThis meta-analysis suggested that current epidemiological studies of TGF-?1 T869C polymorphism are too inconsistent to draw a conclusion on the association with IS susceptibility. Given the small sample size and remarkable between-study heterogeneity, further well-designed prospective large-scale studies are warranted.

Dataset Information

Changes to signal peptide and the level of transforming growth factor- ?1 due to T869C polymorphism of TGF ?1 associated with lupus renal fibrosis.

Publications

Changes to signal peptide and the level of transforming growth factor- β1 due to T869C polymorphism of TGF β1 associated with lupus renal fibrosis.

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