Genetic Variant at the GLUL locus predicts all-cause mortality in patients with type 2 diabetes

Sabrina Prudente, Hetal Shah, Diego Bailetti, Marcus Pezzolesi, Patinut Buranasupkajorn, Luana Mercuri, Christine Mendonca, Salvatore De Cosmo, Monika Niewczas, Vincenzo Trischitta, Alessandro Doria

Research output: Contribution to journalArticlepeer-review

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 6 5.8 and 7.5 6 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.

Original languageEnglish
Pages (from-to)2658-2663
Number of pages6
JournalDiabetes
Volume64
Issue number7
DOIs
Publication statusPublished - Jul 1 2015

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Fingerprint Dive into the research topics of 'Genetic Variant at the GLUL locus predicts all-cause mortality in patients with type 2 diabetes'. Together they form a unique fingerprint.

Cite this