New susceptibility loci associated with kidney disease in type 1 diabetes
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Sandholm , N , Salem , R M , McKnight , A J , Brennan , E P , Forsblom , C , Isakova , T , McKay , G J , Williams , W W , Sadlier , D M , Mäkinen , V-P , Swan , E J , Palmer , C , Boright , A P , Ahlqvist , E , Deshmukh , H A , Keller , B J , Huang , H , Ahola , A , Dahlström , E H , Gordin , T D , Harjutsalo , V , He , B , Heikkilä , O , Hietala , K , Kytö , J , Lahermo , P , Lehto , M , Lithovius , R , Österholm , A-M , Parkkonen , M , Pitkäniemi , J M , Rosengård-Bärlund , M , Saraheimo , M , Sarti , C , Söderlun , J , Soro-Paavonen , A , Syreeni , A , Thorn , L , Tikkanen , H O , Tolonen , N E , Tryggvason , K , Tuomilehto , J , Waden , J , Gill , G V , Prior , S , Guiducci , C , Mirel , D B , Taylor , A , Hosseini , S M , EDIC Research Group , DCCT , Parving , H-H , Rossing , P , Tarnow , L , Ladenvall , C , Alhenc-Gelas , F , Lefebvre , P , Rigalleau , V , Roussel , R , Tregouet , D-A , Maestroni , A , Falhammar , H , Gu , T , Möllsten , A , Cimponeriu , D , Ioana , M , Mota , M , Mota , E , Serafinceanu , C , Stavarachi , M , Hanson , R L , Nelson , R G , Kretzler , M , Colhoun , H M , Panduru , N M , Gu , H F , Brismar , K , Zerbini , G , Hadjadj , S , Marre , M , Groop , L , Lajer , M , Bull , S B , Waggott , D , Paterson , A D , Savage , D A , Bain , S C , Martin , F , Hirschhorn , J N , Godson , C , Florez , J C , Groop , P H , Maxwell , A P & Panduru , N M 2012 , ' New susceptibility loci associated with kidney disease in type 1 diabetes ' , PLoS Genetics , vol. 8 , no. 9 , pp. e1002921 . https://doi.org/10.1371/journal.pgen.1002921
| Julkaisun nimi: | New susceptibility loci associated with kidney disease in type 1 diabetes |
| Tekijä: | Sandholm, Niina; Salem, Rany M.; McKnight, Amy Jayne; Brennan, Eoin P.; Forsblom, Carol; Isakova, Tamara; McKay, Gareth J.; Williams, Winfred W.; Sadlier, Denise M.; Mäkinen, Ville-Petteri; Swan, Elizabeth J.; Palmer, Cameron; Boright, Andrew P.; Ahlqvist, Emma; Deshmukh, Harshal A.; Keller, Benjamin J.; Huang, Huateng; Ahola, Aila; Dahlström, Emma Helena; Gordin, Ted Daniel; Harjutsalo, Valma; He, Bing; Heikkilä, Outi; Hietala, Kustaa; Kytö, Janne; Lahermo, Päivi; Lehto, Markku; Lithovius, Raija; Österholm, Anne-May; Parkkonen, Maija; Pitkäniemi, Janne Mikael; Rosengård-Bärlund, Milla; Saraheimo, Markku; Sarti, Cinzia; Söderlun, Jenny; Soro-Paavonen, Aino; Syreeni, Anna; Thorn, Lena; Tikkanen, Heikki Olavi; Tolonen, Nina Emilia; Tryggvason, Karl; Tuomilehto, Jaakko; Waden, Johan; Gill, Geoffrey V.; Prior, Sarah; Guiducci, Candace; Mirel, Daniel B.; Taylor, Andrew; Hosseini, S. Mohsen; EDIC Research Group, DCCT/; Parving, Hans-Henrik; Rossing, Peter; Tarnow, Lise; Ladenvall, Claes; Alhenc-Gelas, Francois; Lefebvre, Pierre; Rigalleau, Vincent; Roussel, Ronan; Tregouet, David-Alexandre; Maestroni, Anna; Falhammar, Henrik; Gu, Tianwei; Möllsten, Anna; Cimponeriu, Danut; Ioana, Mihai; Mota, Maria; Mota, Eugen; Serafinceanu, Cristian; Stavarachi, Monica; Hanson, Robert L.; Nelson, Robert G.; Kretzler, Matthias; Colhoun, Helen M.; Panduru, Nicolae Mircea; Gu, Harvest F.; Brismar, Kerstin; Zerbini, Gianpaolo; Hadjadj, Samy; Marre, Michel; Groop, Leif; Lajer, Maria; Bull, Shelley B.; Waggott, Daryl; Paterson, Andrew D.; Savage, David A.; Bain, Stephen C.; Martin, Finian; Hirschhorn, Joel N.; Godson, Catherine; Florez, Jose C.; Groop, Per Henrik; Maxwell, Alexander P.; Panduru, Nicolae Mircea |
| Tekijän organisaatio: | Department of Medicine Nefrologian yksikkö Department of Medical and Clinical Genetics HUS Internal Medicine and Rehabilitation HUS Abdominal Center Doctoral Programme in Clinical Research Department of Ophthalmology and Otorhinolaryngology Silmäklinikka Institute for Molecular Medicine Finland Hjelt Institute (-2014) Department of Public Health Clinicum |
| Päiväys: | 2012 |
| Kieli: | eng |
| Sivumäärä: | 24 |
| Kuuluu julkaisusarjaan: | PLoS Genetics |
| ISSN: | 1553-7390 |
| DOI-tunniste: | https://doi.org/10.1371/journal.pgen.1002921 |
| URI: | http://hdl.handle.net/10138/162537 |
| Tiivistelmä: | 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 genome-wide association studies (GWAS) of T1D DN comprising ∼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 = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-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. |
| Kuvaus: | WOS:000309817900008 |
| Avainsanat: |
3142 Public health care science, environmental and occupational health
type 1 diabetes kideny disease 3121 General medicine, internal medicine and other clinical medicine |
| Vertaisarvioitu: | Kyllä |
| Tekijänoikeustiedot: | cc_by |
| Pääsyrajoitteet: | openAccess |
| Rinnakkaistallennettu versio: | publishedVersion |
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