Evidence map›Paper›PMID 29204904›Full record

ArticleClinical and experimental nephrology2018

The functionality of African-specific variants in the TGFB1 regulatory region and their potential role in HIVAN.

M Nel, J-M Buys, F C J Botha, N Wearne, S Prince, J M Heckmann

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Article in Clinical and experimental nephrology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 44% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 3 citations in OpenAlex.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

M Nel *Neurology Research Group, Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
J-M Buys *Neurology Research Group, Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
F C J BothaDivision of Anatomical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
N WearneDivision of Nephrology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
S PrinceDivision of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa.
J M HeckmannNeurology Research Group, Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa. Jeanine.heckmann@uct.ac.za.ORCID http://orcid.org/0000-0002-8999-718X
University of Cape Town · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTranscription of transforming growth factor beta-1 (TGF-β1) is regulated by a polymorphic promoter region containing African-specific single nucleotide polymorphisms (SNPs). Some of these SNPs have higher frequencies among Southern Africans compared to other African populations and their functionality has only been partially studied. Due to the high prevalence of HIV-associated nephropathy (HIVAN) in Africans we hypothesized that functional African TGFB1-promoter SNPs may contribute to HIVAN pathogenesis.

methodsThe functionality of the TGFB1 -1347 C>T variant and African-specific variants (-1287 G>A, -1154 C>T, -387 C>T and -14 G>A) were examined by measuring reporter gene expression in kidney and fibroblast cell lines co-transfected with TGFB1-promoter constructs and an HIV-Tat expression vector. TGF-β1 immunohistochemical staining was performed on kidney biopsies with HIVAN (n = 18) and compared to control biopsies without HIVAN or tubulointerstitial disease (n = 12) using semi-quantitative and digital image analysis. HIVAN cases were genotyped for TGFB1 -1347 and -387 SNP variants.

resultsTGFB1-promoter haplotypes containing the African -387 T-allele resulted in ~ five-fold repression of TGFB1-promoter activity compared to -387 C haplotypes (p ≤ 0.024). HIV-Tat upregulated TGFB1-promoter activity for haplotypes containing -1347 T and -387 T in transfected renal cells (≈ 1.6-fold; p ≤ 0.030) and fibroblasts (≈ 1.3-fold; p ≤ 0.016). The renal interstitium from HIVAN biopsies, compared to HIV-positive and -negative controls, differed in the semi-quantitative TGF-β1 staining and digital optical density analyses. The TGFB1 -1347 and -387 genotypes in HIVAN cases were similar to population controls.

conclusionAfrican-specific haplotypes lower TGFB1-promoter activity and expression levels and HIV-Tat upregulates TGFB1 promoter activity irrespective of the haplotype.

Indexed as

Regulatory Sequences, Nucleic AcidAfricaAIDS-Associated NephropathyCell LineFibroblastsHaplotypesHumansKidneyPolymorphism, Single NucleotideTransforming Growth Factor beta1TGFB1 protein, humanTransforming Growth Factor beta1AfricaHIVANKidneyPolymorphismPromoterTransforming growth factor B1

Identifiers

PMID29204904
OpenAlexW2774623112

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.