Carlo-Stella N, Bozzini S, De Silvestri A, Sbarsi I, Pizzochero C, Lorusso L, Martinetti M, Cuccia M
Genetics and Microbiology Department, University of Pavia, Pavia, Italy.
Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):745-54. doi: 10.1177/039463200902200320.
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-DRB111 and DRB113 alleles. The haplotypes RAGE-374T, DRB104; RAGE-374T, DRB109; RAGE-374T, DRB111; RAGE-374A, DRB113; RAGE-429T, DRB104 and RAGE-429C, DRB111 were significantly more frequent in CFS patients, whereas RAGE-429C, DRB107 would seem protective. A significantly lower frequency of DRB11104 (5.4% vs 12.9% p=0.04, OR=0.39) and a significantly higher frequency of HLA-DRB11301 (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-DRB11104 (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.
晚期糖基化终末产物受体（RAGE）被认为在炎症中起重要作用。慢性疲劳综合征（CFS）是一种长期疲劳，在无其他已知病因的情况下，至少影响受试者50%的日常活动。免疫功能障碍与之相关，且发现其与一种特殊的基因细胞因子谱有关，这种谱易引发炎症性质的免疫调节反应。本研究的目的是分析75例意大利CFS患者以及141例年龄、性别和种族相匹配的对照者的RAGE基因多态性和HLA - DRB1等位基因。这两组人群接受了RAGE基因374T/A和429C/T启动子多态性的基因组研究；此外，46例患者和186例对照者进行了低分辨率分子水平的HLA - DRB1分型。其中，31例患者和99例对照者还进行了高分辨率分析以确定HLA - DRB111和DRB113等位基因。单倍型RAGE - 374T，DRB104；RAGE - 374T，DRB109；RAGE - 374T，DRB111；RAGE - 374A，DRB113；RAGE - 429T，DRB104和RAGE - 429C，DRB111在CFS患者中显著更常见，而RAGE - 429C，DRB107似乎具有保护作用。在CFS患者中发现DRB11104的频率显著更低（5.4%对12.9%，p = 0.04，OR = 0.39），而HLA - DRB11301的频率显著更高（13.0%对5.1%，p = 0.006，OR = 2.79）。观察到RAGE基因多态性具有协同效应。在以下顺式组合中OR值增强：RAGE - 374A，HLA - DRB11104（OR = 0.27）和RAGE - 374A，HLA - DRB1*1301（OR = 6.23）。似乎是HLA单倍型而非RAGE或DRB1基因的单个等位基因参与了CFS，可能涉及一个主要感兴趣的亚区域。
