TY - JOUR
T1 - Genetic Variant at the GLUL locus predicts all-cause mortality in patients with type 2 diabetes
AU - Prudente, Sabrina
AU - Shah, Hetal
AU - Bailetti, Diego
AU - Pezzolesi, Marcus
AU - Buranasupkajorn, Patinut
AU - Mercuri, Luana
AU - Mendonca, Christine
AU - De Cosmo, Salvatore
AU - Niewczas, Monika
AU - Trischitta, Vincenzo
AU - Doria, Alessandro
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
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U2 - 10.2337/db14-1653
DO - 10.2337/db14-1653
M3 - Article
C2 - 25677913
AN - SCOPUS:84962124849
SN - 0012-1797
VL - 64
SP - 2658
EP - 2663
JO - Diabetes
JF - Diabetes
IS - 7
ER -