title: Genetic Variant at the GLUL Locus Predicts All-Cause Mortality in Patients With Type 2 Diabetes.
abstract: 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.
authors: Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Mendel Laboratory, San Giovanni Rotondo, Italy.
authors: Sabrina
authors: S
authors: Prudente
authors: Research Division, Joslin Diabetes Center, Boston, MA Department of Medicine, Harvard Medical School, Boston, MA.
authors: Hetal
authors: H
authors: Shah
authors: Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Mendel Laboratory, San Giovanni Rotondo, Italy Department of Experimental Medicine, Sapienza University, Rome, Italy.
authors: Diego
authors: D
authors: Bailetti
authors: Research Division, Joslin Diabetes Center, Boston, MA Department of Medicine, Harvard Medical School, Boston, MA.
authors: Marcus
authors: M
authors: Pezzolesi
authors: Research Division, Joslin Diabetes Center, Boston, MA Department of Medicine, Harvard Medical School, Boston, MA.
authors: Patinut
authors: P
authors: Buranasupkajorn
authors: Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Mendel Laboratory, San Giovanni Rotondo, Italy.
authors: Luana
authors: L
authors: Mercuri
authors: Research Division, Joslin Diabetes Center, Boston, MA.
authors: Christine
authors: C
authors: Mendonca
authors: Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Department of Medicine, San Giovanni Rotondo, Italy.
authors: Salvatore
authors: S
authors: De Cosmo
authors: Research Division, Joslin Diabetes Center, Boston, MA Department of Medicine, Harvard Medical School, Boston, MA.
authors: Monika
authors: M
authors: Niewczas
authors: Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Mendel Laboratory, San Giovanni Rotondo, Italy Department of Experimental Medicine, Sapienza University, Rome, Italy Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Research Unit of Diabetes and Endocrine Diseases, San Giovanni Rotondo, Italy.
authors: Vincenzo
authors: V
authors: Trischitta
authors: Research Division, Joslin Diabetes Center, Boston, MA Department of Medicine, Harvard Medical School, Boston, MA alessandro.doria@joslin.harvard.edu.
authors: Alessandro
authors: A
authors: Doria
mesh_terms: D000328:Adult; D000368:Aged; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000401:mortality; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D005974:Glutamate-Ammonia Ligase