UNLABELLED: Activation of the receptor for advanced glycation end-products (RAGE) leads to a cascade of pro-inflammatory and pro-coagulant responses which are important in the pathogenesis of the vascular complications of diabetes mellitus. It is known that pro-inflammatory mechanisms underpin the development of type 2 diabetes. Our hypothesis is that RAGE may be involved in the evolution of insulin resistance in addition to mediating glucotoxic complications of diabetes mellitus. METHODS: To investigate the relationship between RAGE allelic variation and insulin resistance, the Gly82Ser variant and three promoter variants (-429, -374, 63 bp deletion) were studied in 480 subjects of known relationship from 89 families characterised for insulin resistance (using homeostasis model assessment [HOMA]) and for atherothrombotic risk. Carriage of the -429 C allele was weakly associated with increased insulin resistance (p = 0.02) when pedigree analysis was performed using SOLAR software. RESULTS: Insulin resistance was estimated to have a heritability of 25.8% before the addition of covariates. Analysis of the relationship between RAGE and insulin resistance indicated that the -429 polymorphism reduced the unexplained heritability of insulin resistance after adjusting for covariates (age, sex, body mass index) from 17.5% of the total variance to 15.6% of the total variance. CONCLUSIONS: These preliminary results indicate that the RAGE gene may affect the development of insulin resistance or be in linkage disequilibrium with a locus involved in this process.
UNLABELLED: Activation of the receptor for advanced glycation end-products (RAGE) leads to a cascade of pro-inflammatory and pro-coagulant responses which are important in the pathogenesis of the vascular complications of diabetes mellitus. It is known that pro-inflammatory mechanisms underpin the development of type 2 diabetes. Our hypothesis is that RAGE may be involved in the evolution of insulin resistance in addition to mediating glucotoxic complications of diabetes mellitus. METHODS: To investigate the relationship between RAGE allelic variation and insulin resistance, the Gly82Ser variant and three promoter variants (-429, -374, 63 bp deletion) were studied in 480 subjects of known relationship from 89 families characterised for insulin resistance (using homeostasis model assessment [HOMA]) and for atherothrombotic risk. Carriage of the -429 C allele was weakly associated with increased insulin resistance (p = 0.02) when pedigree analysis was performed using SOLAR software. RESULTS:Insulin resistance was estimated to have a heritability of 25.8% before the addition of covariates. Analysis of the relationship between RAGE and insulin resistance indicated that the -429 polymorphism reduced the unexplained heritability of insulin resistance after adjusting for covariates (age, sex, body mass index) from 17.5% of the total variance to 15.6% of the total variance. CONCLUSIONS: These preliminary results indicate that the RAGE gene may affect the development of insulin resistance or be in linkage disequilibrium with a locus involved in this process.
Authors: Lisa L Morselli; Eric R Gamazon; Esra Tasali; Nancy J Cox; Eve Van Cauter; Lea K Davis Journal: Diabetes Date: 2017-10-30 Impact factor: 9.461
Authors: A P Gjesing; C T Ekstrøm; H Eiberg; S A Urhammer; J J Holst; O Pedersen; T Hansen Journal: Diabetologia Date: 2012-02-15 Impact factor: 10.122
Authors: J M Forbes; J Söderlund; F Y T Yap; M Knip; S Andrikopoulos; J Ilonen; O Simell; R Veijola; K C Sourris; M T Coughlan; C Forsblom; R Slattery; S T Grey; M Wessman; H Yamamoto; A Bierhaus; M E Cooper; P-H Groop Journal: Diabetologia Date: 2011-02-06 Impact factor: 10.122
Authors: Sonya J Elder; Alice H Lichtenstein; Anastassios G Pittas; Susan B Roberts; Paul J Fuss; Andrew S Greenberg; Megan A McCrory; Thomas J Bouchard; Edward Saltzman; Michael C Neale Journal: J Lipid Res Date: 2009-04-16 Impact factor: 5.922