umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
New susceptibility loci associated with kidney disease in type 1 diabetes
Show others and affiliations
2012 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 8, no 9, e1002921- p.Article in journal (Refereed) Published
Abstract [en]

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Place, publisher, year, edition, pages
San Francisco, USA: Public Library of Science, PLOS , 2012. Vol. 8, no 9, e1002921- p.
Keyword [en]
GENOME-WIDE ASSOCIATION, RENAL-FUNCTION, NATURAL-HISTORY, COLLAGEN CHAINS, AF4/FMR2 FAMILY, GROWTH-FACTOR, NEPHROPATHY, EXPRESSION, RISK, GENE
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Genetics
Identifiers
URN: urn:nbn:se:umu:diva-61788DOI: 10.1371/journal.pgen.1002921ISI: 000309817900008OAI: oai:DiVA.org:umu-61788DiVA: diva2:572462
Available from: 2012-11-27 Created: 2012-11-26 Last updated: 2017-12-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Mollsten, Anna
By organisation
Paediatrics
In the same journal
PLOS Genetics
Public Health, Global Health, Social Medicine and Epidemiology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 131 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf