Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in chronic fatigue syndrome

N. Carlo-Stella, S. Bozzini, A. De Silvestri, I. Sbarsi, C. Pizzochero, L. Lorusso, M. Martinetti, Mariaclara Cuccia

Research output: Contribution to journalArticlepeer-review

Abstract

The receptor for advanced glycation end product (RAGE) is thought to play an important role in inflammation. Chronic Fatigue Syndrome (CFS) is a long-lasting fatigue that compromises at least 50% of a subject's daily activities without other known cause. Immune dysfunction has been implicated and an association with a peculiar genetic cytokine profile, predisposing to an immunomodulatory response of inflammatory nature, was found. The aim of this study is to analyse RAGE polymorphisms and HLA-DRB1 alleles in seventy-five Italian CFS patients and 141 controls matched for age, sex and ethnicity. These two groups underwent genomic study for RAGE -374T/A and -429C/T promoter polymorphisms; moreover, 46 patients and 186 controls were typed for HLA-DRB1 at low resolution molecular level. Of these, 31 patients and 99 controls also underwent "high resolution analysis" to define the HLA-DRB1*11 and DRB1*13 alleles. The haplotypes RAGE-374T, DRB1*04; RAGE-374T, DRB1*09; RAGE-374T, DRB1*11; RAGE-374A, DRB1*13; RAGE-429T, DRB1*04 and RAGE-429C, DRB1*11 were significantly more frequent in CFS patients, whereas RAGE-429C, DRB1*07 would seem protective. A significantly lower frequency of DRB1*1104 (5.4% vs 12.9% p=0.04, OR=0.39) and a significantly higher frequency of HLA-DRB1*1301 (13.0% vs 5.1% p=0.006, OR=2.79) were found in CFS patients. A synergic effect was observed with RAGE polymorphism. The OR values strengthened in the following cis combinations: RAGE-374A, HLA-DRB1*1104 (OR=0.27) and RAGE-374A, HLA-DRB1*1301 (OR=6.23). HLA haplotypes rather than single alleles of RAGE or of DRB1 genes seem to be involved in CFS, probably including a subregion of major interest.

Original languageEnglish
Pages (from-to)745-754
Number of pages10
JournalInternational Journal of Immunopathology and Pharmacology
Volume22
Issue number3
Publication statusPublished - Jul 2009

Keywords

  • Chronic fatigue syndrome
  • Haplotypes
  • HLA
  • Linkage disequilibrium
  • RAGE

ASJC Scopus subject areas

  • Pharmacology
  • Immunology
  • Immunology and Allergy

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