Cargando…

Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes

Single nucleotide polymorphism (SNP) rs10911021 at the glutamate-ammonia ligase (GLUL) locus has been associated with an increased risk of coronary heart disease in individuals with type 2 diabetes. The effect of this SNP on mortality was investigated among 1,242 white subjects with type 2 diabetes...

Descripción completa

Detalles Bibliográficos
Autores principales: Prudente, Sabrina, Shah, Hetal, Bailetti, Diego, Pezzolesi, Marcus, Buranasupkajorn, Patinut, Mercuri, Luana, Mendonca, Christine, De Cosmo, Salvatore, Niewczas, Monika, Trischitta, Vincenzo, Doria, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477355/
https://www.ncbi.nlm.nih.gov/pubmed/25677913
http://dx.doi.org/10.2337/db14-1653
_version_ 1782377741863092224
author Prudente, Sabrina
Shah, Hetal
Bailetti, Diego
Pezzolesi, Marcus
Buranasupkajorn, Patinut
Mercuri, Luana
Mendonca, Christine
De Cosmo, Salvatore
Niewczas, Monika
Trischitta, Vincenzo
Doria, Alessandro
author_facet Prudente, Sabrina
Shah, Hetal
Bailetti, Diego
Pezzolesi, Marcus
Buranasupkajorn, Patinut
Mercuri, Luana
Mendonca, Christine
De Cosmo, Salvatore
Niewczas, Monika
Trischitta, Vincenzo
Doria, Alessandro
author_sort Prudente, Sabrina
collection PubMed
description Single nucleotide polymorphism (SNP) rs10911021 at the glutamate-ammonia ligase (GLUL) locus has been associated with an increased risk of coronary heart disease in individuals with type 2 diabetes. The effect of this SNP on mortality was investigated among 1,242 white subjects with type 2 diabetes from the Joslin Kidney Study (JKS) (n = 416) and the Gargano Mortality Study (GMS) (n = 826). During a mean follow-up of 12.8 ± 5.8 and 7.5 ± 2.2 years, respectively, a total of 215 and 164 deaths were observed in the two studies. In both cohorts, the all-cause mortality rate significantly increased with the number of rs10911021 risk alleles, with allelic hazard ratios (HRs) of 1.32 (95% CI 1.07–1.64, P = 0.01), 1.30 (1.10–1.69, P = 0.04), and 1.32 (1.12–1.55, P = 0.0011), respectively, in the JKS, the GMS, and the two studies combined. These associations were not affected by adjustment for possible confounders. In the JKS, for which data on causes of death were available, the HR for cardiovascular mortality was 1.51 (1.12–2.04, P = 0.0077) as opposed to 1.15 (0.84–1.55, P = 0.39) for mortality from noncardiovascular causes. These findings point to SNP rs10911021 as an independent modulator of mortality in patients with type 2 diabetes and, together with the previous observation, suggest that this results from an effect of this variant on cardiovascular risk.
format Online
Article
Text
id pubmed-4477355
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-44773552016-07-01 Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes Prudente, Sabrina Shah, Hetal Bailetti, Diego Pezzolesi, Marcus Buranasupkajorn, Patinut Mercuri, Luana Mendonca, Christine De Cosmo, Salvatore Niewczas, Monika Trischitta, Vincenzo Doria, Alessandro Diabetes Genetics/Genomes/Proteomics/Metabolomics Single nucleotide polymorphism (SNP) rs10911021 at the glutamate-ammonia ligase (GLUL) locus has been associated with an increased risk of coronary heart disease in individuals with type 2 diabetes. The effect of this SNP on mortality was investigated among 1,242 white subjects with type 2 diabetes from the Joslin Kidney Study (JKS) (n = 416) and the Gargano Mortality Study (GMS) (n = 826). During a mean follow-up of 12.8 ± 5.8 and 7.5 ± 2.2 years, respectively, a total of 215 and 164 deaths were observed in the two studies. In both cohorts, the all-cause mortality rate significantly increased with the number of rs10911021 risk alleles, with allelic hazard ratios (HRs) of 1.32 (95% CI 1.07–1.64, P = 0.01), 1.30 (1.10–1.69, P = 0.04), and 1.32 (1.12–1.55, P = 0.0011), respectively, in the JKS, the GMS, and the two studies combined. These associations were not affected by adjustment for possible confounders. In the JKS, for which data on causes of death were available, the HR for cardiovascular mortality was 1.51 (1.12–2.04, P = 0.0077) as opposed to 1.15 (0.84–1.55, P = 0.39) for mortality from noncardiovascular causes. These findings point to SNP rs10911021 as an independent modulator of mortality in patients with type 2 diabetes and, together with the previous observation, suggest that this results from an effect of this variant on cardiovascular risk. American Diabetes Association 2015-07 2015-02-12 /pmc/articles/PMC4477355/ /pubmed/25677913 http://dx.doi.org/10.2337/db14-1653 Text en © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Prudente, Sabrina
Shah, Hetal
Bailetti, Diego
Pezzolesi, Marcus
Buranasupkajorn, Patinut
Mercuri, Luana
Mendonca, Christine
De Cosmo, Salvatore
Niewczas, Monika
Trischitta, Vincenzo
Doria, Alessandro
Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes
title Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes
title_full Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes
title_fullStr Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes
title_full_unstemmed Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes
title_short Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes
title_sort genetic variant at the glul locus predicts all-cause mortality in patients with type 2 diabetes
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477355/
https://www.ncbi.nlm.nih.gov/pubmed/25677913
http://dx.doi.org/10.2337/db14-1653
work_keys_str_mv AT prudentesabrina geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT shahhetal geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT bailettidiego geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT pezzolesimarcus geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT buranasupkajornpatinut geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT mercuriluana geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT mendoncachristine geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT decosmosalvatore geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT niewczasmonika geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT trischittavincenzo geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes
AT doriaalessandro geneticvariantattheglullocuspredictsallcausemortalityinpatientswithtype2diabetes