title: Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in chronic fatigue syndrome.
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, HLADRB1*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.
authors.affiliation: Genetics and Microbiology Department, University of Pavia, Pavia, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Carlo-Stella
authors.forename: S
authors.initials: S
authors.lastname: Bozzini
authors.forename: A
authors.initials: A
authors.lastname: De Silvestri
authors.forename: I
authors.initials: I
authors.lastname: Sbarsi
authors.forename: C
authors.initials: C
authors.lastname: Pizzochero
authors.forename: L
authors.initials: L
authors.lastname: Lorusso
authors.forename: M
authors.initials: M
authors.lastname: Martinetti
authors.forename: M
authors.initials: M
authors.lastname: Cuccia
mesh_terms: D016022:Case-Control Studies; D015673:Fatigue Syndrome, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic