Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes

Abstract Urinary albumin excretion is an early sign of diabetic kidney disease, affecting every third individual with diabetes. Despite substantial estimated heritability, only variants in the GLRA3 gene have been genome-wide significantly associated (p-value < 5 × 10−8) with diabetic albuminuria...

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Autores principales:	Niina Sandholm, Jani K Haukka, Iiro Toppila, Erkka Valo, Valma Harjutsalo, Carol Forsblom, Per-Henrik Groop
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86e9a250dc08488f9a5488cfa33be9b5
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spelling	oai:doaj.org-article:86e9a250dc08488f9a5488cfa33be9b52021-12-02T15:07:44ZConfirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes10.1038/s41598-018-29211-12045-2322https://doaj.org/article/86e9a250dc08488f9a5488cfa33be9b52018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29211-1https://doaj.org/toc/2045-2322Abstract Urinary albumin excretion is an early sign of diabetic kidney disease, affecting every third individual with diabetes. Despite substantial estimated heritability, only variants in the GLRA3 gene have been genome-wide significantly associated (p-value < 5 × 10−8) with diabetic albuminuria, in Finnish individuals with type 1 diabetes; However, replication attempt in non-Finnish Europeans with type 1 diabetes showed nominally significant association in the opposite direction, suggesting a population-specific effect, but simultaneously leaving the finding controversial. In this study, the association between the common rs10011025 variant in the GLRA3 locus, and albuminuria, was confirmed in 1259 independent Finnish individuals with type 1 diabetes (p = 0.0013), and meta-analysis of all Finnish individuals yielded a genome-wide significant association. The association was particularly pronounced in subjects not reaching the treatment target for blood glucose levels (HbA1c > 7%; N = 2560, p = 1.7 × 10−9). Even though further studies are needed to pinpoint the causal variants, dissecting the association at the GLRA3 locus may uncover novel molecular mechanisms for diabetic albuminuria irrespective of population background.Niina SandholmJani K HaukkaIiro ToppilaErkka ValoValma HarjutsaloCarol ForsblomPer-Henrik GroopNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Niina Sandholm Jani K Haukka Iiro Toppila Erkka Valo Valma Harjutsalo Carol Forsblom Per-Henrik Groop Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes
description	Abstract Urinary albumin excretion is an early sign of diabetic kidney disease, affecting every third individual with diabetes. Despite substantial estimated heritability, only variants in the GLRA3 gene have been genome-wide significantly associated (p-value < 5 × 10−8) with diabetic albuminuria, in Finnish individuals with type 1 diabetes; However, replication attempt in non-Finnish Europeans with type 1 diabetes showed nominally significant association in the opposite direction, suggesting a population-specific effect, but simultaneously leaving the finding controversial. In this study, the association between the common rs10011025 variant in the GLRA3 locus, and albuminuria, was confirmed in 1259 independent Finnish individuals with type 1 diabetes (p = 0.0013), and meta-analysis of all Finnish individuals yielded a genome-wide significant association. The association was particularly pronounced in subjects not reaching the treatment target for blood glucose levels (HbA1c > 7%; N = 2560, p = 1.7 × 10−9). Even though further studies are needed to pinpoint the causal variants, dissecting the association at the GLRA3 locus may uncover novel molecular mechanisms for diabetic albuminuria irrespective of population background.
format	article
author	Niina Sandholm Jani K Haukka Iiro Toppila Erkka Valo Valma Harjutsalo Carol Forsblom Per-Henrik Groop
author_facet	Niina Sandholm Jani K Haukka Iiro Toppila Erkka Valo Valma Harjutsalo Carol Forsblom Per-Henrik Groop
author_sort	Niina Sandholm
title	Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes
title_short	Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes
title_full	Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes
title_fullStr	Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes
title_full_unstemmed	Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes
title_sort	confirmation of glra3 as a susceptibility locus for albuminuria in finnish patients with type 1 diabetes
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/86e9a250dc08488f9a5488cfa33be9b5
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Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes

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