RAGE polymorphisms and the heritability of insulin resistance: The Leeds Family Study

Clair M. Sullivan, T. Simon Futers, Jennifer H. Barrett, Barry Hudson, Mark S. Freeman, Peter J. Grant

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)42-44
Number of pages3
JournalDiabetes and Vascular Disease Research
Volume2
Issue number1
StatePublished - Feb 1 2005
Externally publishedYes

Fingerprint

Insulin Resistance
Diabetes Complications
Coagulants
Advanced Glycosylation End Product-Specific Receptor
Linkage Disequilibrium
Pedigree
Type 2 Diabetes Mellitus
Blood Vessels
Body Mass Index
Homeostasis
Software
Alleles
Genes

Keywords

  • Advanced glycation end-products
  • Insulin resistance
  • Polymorphism
  • Population studies
  • RAGE

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Sullivan, C. M., Futers, T. S., Barrett, J. H., Hudson, B., Freeman, M. S., & Grant, P. J. (2005). RAGE polymorphisms and the heritability of insulin resistance: The Leeds Family Study. Diabetes and Vascular Disease Research, 2(1), 42-44.

RAGE polymorphisms and the heritability of insulin resistance : The Leeds Family Study. / Sullivan, Clair M.; Futers, T. Simon; Barrett, Jennifer H.; Hudson, Barry; Freeman, Mark S.; Grant, Peter J.

In: Diabetes and Vascular Disease Research, Vol. 2, No. 1, 01.02.2005, p. 42-44.

Research output: Contribution to journalArticle

Sullivan, CM, Futers, TS, Barrett, JH, Hudson, B, Freeman, MS & Grant, PJ 2005, 'RAGE polymorphisms and the heritability of insulin resistance: The Leeds Family Study', Diabetes and Vascular Disease Research, vol. 2, no. 1, pp. 42-44.
Sullivan, Clair M. ; Futers, T. Simon ; Barrett, Jennifer H. ; Hudson, Barry ; Freeman, Mark S. ; Grant, Peter J. / RAGE polymorphisms and the heritability of insulin resistance : The Leeds Family Study. In: Diabetes and Vascular Disease Research. 2005 ; Vol. 2, No. 1. pp. 42-44.
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