Joint effect of insulin signaling genes on all-cause mortality

Claudia Menzaghi, Andrea Fontana, Massimiliano Copetti, Stefano Rizza, Belinda Spoto, Patinut Buranasupkajorn, Giovanni Tripepi, Antonella Marucci, Diego Bailetti, Timothy Hastings, Alessandra Testa, Christine Mendonca, Francesca Mallamaci, Salvatore De Cosmo, Simonetta Bacci, Massimo Federici, Alessandro Doria, Carmine Zoccali, Vincenzo Trischitta

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: We have previously reported the combined effect of SNPs perturbing insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular events We here investigated whether such a combined effect affects also all-cause mortality in a sample of 1851 Whites of European ancestry Methods: We investigated a first sample of 721 patients, 232 deaths, 3389 person-years (py) Replication was assessed in two samples of patients with T2D: the Gargano Mortality Study (GMS) of 714 patients, 127 deaths, 5426py and the Joslin Kidney Study (JKS) comprising 416 patients, 214 deaths, 5325py Results: In the first sample, individuals carrying 1 or ≥2 risk alleles had 33% (p=0.06) and 51% (p=0.02) increased risk of mortality, as compared with individuals with no risk alleles A similar, though not significant, trend was obtained in the two replication samples only for subject carrying≥2 risk alleles In a pooled analysis, individuals carrying ≥2 risk alleles had higher mortality rate as compared to those carrying 0 risk alleles (HR=1.34, 95%CI=1.08-1.67; p=0.008), and as compared to those carrying only one risk allele (HR=1.41, 95%CI=1.13-1.75; p=0.002) This association was independent from several possible confounders including sex, age, BMI, hypertension and diabetes status Conclusion: Our data suggest that variants affecting insulin signaling exert a joint effect on all-cause mortality and is consistent with a role of abnormal insulin signaling on mortality risk

Original languageEnglish
Pages (from-to)639-644
Number of pages6
JournalAtherosclerosis
Volume237
Issue number2
DOIs
Publication statusPublished - Dec 1 2014

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Insulin
Mortality
Alleles
Genes
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Insulin Resistance
Hypertension
Kidney

Keywords

  • ENPP1
  • IRS1
  • Prospective study
  • TRIB3

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Joint effect of insulin signaling genes on all-cause mortality. / Menzaghi, Claudia; Fontana, Andrea; Copetti, Massimiliano; Rizza, Stefano; Spoto, Belinda; Buranasupkajorn, Patinut; Tripepi, Giovanni; Marucci, Antonella; Bailetti, Diego; Hastings, Timothy; Testa, Alessandra; Mendonca, Christine; Mallamaci, Francesca; De Cosmo, Salvatore; Bacci, Simonetta; Federici, Massimo; Doria, Alessandro; Zoccali, Carmine; Trischitta, Vincenzo.

In: Atherosclerosis, Vol. 237, No. 2, 01.12.2014, p. 639-644.

Research output: Contribution to journalArticle

Menzaghi, C, Fontana, A, Copetti, M, Rizza, S, Spoto, B, Buranasupkajorn, P, Tripepi, G, Marucci, A, Bailetti, D, Hastings, T, Testa, A, Mendonca, C, Mallamaci, F, De Cosmo, S, Bacci, S, Federici, M, Doria, A, Zoccali, C & Trischitta, V 2014, 'Joint effect of insulin signaling genes on all-cause mortality', Atherosclerosis, vol. 237, no. 2, pp. 639-644. https://doi.org/10.1016/j.atherosclerosis.2014.10.005
Menzaghi, Claudia ; Fontana, Andrea ; Copetti, Massimiliano ; Rizza, Stefano ; Spoto, Belinda ; Buranasupkajorn, Patinut ; Tripepi, Giovanni ; Marucci, Antonella ; Bailetti, Diego ; Hastings, Timothy ; Testa, Alessandra ; Mendonca, Christine ; Mallamaci, Francesca ; De Cosmo, Salvatore ; Bacci, Simonetta ; Federici, Massimo ; Doria, Alessandro ; Zoccali, Carmine ; Trischitta, Vincenzo. / Joint effect of insulin signaling genes on all-cause mortality. In: Atherosclerosis. 2014 ; Vol. 237, No. 2. pp. 639-644.
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AU - Fontana, Andrea

AU - Copetti, Massimiliano

AU - Rizza, Stefano

AU - Spoto, Belinda

AU - Buranasupkajorn, Patinut

AU - Tripepi, Giovanni

AU - Marucci, Antonella

AU - Bailetti, Diego

AU - Hastings, Timothy

AU - Testa, Alessandra

AU - Mendonca, Christine

AU - Mallamaci, Francesca

AU - De Cosmo, Salvatore

AU - Bacci, Simonetta

AU - Federici, Massimo

AU - Doria, Alessandro

AU - Zoccali, Carmine

AU - Trischitta, Vincenzo

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N2 - Objective: We have previously reported the combined effect of SNPs perturbing insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular events We here investigated whether such a combined effect affects also all-cause mortality in a sample of 1851 Whites of European ancestry Methods: We investigated a first sample of 721 patients, 232 deaths, 3389 person-years (py) Replication was assessed in two samples of patients with T2D: the Gargano Mortality Study (GMS) of 714 patients, 127 deaths, 5426py and the Joslin Kidney Study (JKS) comprising 416 patients, 214 deaths, 5325py Results: In the first sample, individuals carrying 1 or ≥2 risk alleles had 33% (p=0.06) and 51% (p=0.02) increased risk of mortality, as compared with individuals with no risk alleles A similar, though not significant, trend was obtained in the two replication samples only for subject carrying≥2 risk alleles In a pooled analysis, individuals carrying ≥2 risk alleles had higher mortality rate as compared to those carrying 0 risk alleles (HR=1.34, 95%CI=1.08-1.67; p=0.008), and as compared to those carrying only one risk allele (HR=1.41, 95%CI=1.13-1.75; p=0.002) This association was independent from several possible confounders including sex, age, BMI, hypertension and diabetes status Conclusion: Our data suggest that variants affecting insulin signaling exert a joint effect on all-cause mortality and is consistent with a role of abnormal insulin signaling on mortality risk

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