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Correlation between interleukin‐6 promoter and C‐reactive protein (CRP) polymorphisms and CRP levels with the Mainz Severity Score Index for Fabry disease
Author(s) -
Altarescu G.,
Chicco G.,
Whybra C.,
DelgadoSanchez S.,
Sharon N.,
Beck M.,
Elstein D.
Publication year - 2008
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-007-0716-6
Subject(s) - medicine , genotype , c reactive protein , gastroenterology , fabry disease , disease , inflammation , biology , genetics , gene
Summary Objectives: Fabry disease is a multisystem disorder with phenotypic heterogeneity only partially explained by genotype. Elevated interleukin‐6 (IL‐6) plasma levels and C‐reactive protein (CRP) serum levels are associated with increased risk and worse outcome of ischaemic events, a serious prognostic sign in Fabry disease. Methods: 56 patients (34 hemizygous males, 22 females; 5 children) were studied. A promoter polymorphism −174G > C of the IL‐6 gene associated with serum IL‐6 levels was compared with the Mainz Severity Score Index (MSSI) in patients with Fabry disease. CRP levels and polymorphism 1059 G > C were evaluated as markers of inflammation to ascertain the possibility of an inflammatory mechanism of IL‐6. Nonparametric ANOVA, Fisher's exact, Bonferroni, and Hardy–Weinberg (HW) statistics were used. Results: Mean age of adults = 42 (range 26–58) years; 29 patients received enzyme therapy (ERT). Mean total MSSI = 26.7 (range 14.2–39.2) points, i.e. moderate disease, but females were lower (total 23.4 ± 12.6 vs 32.2 ± 13.6). Controls but not patients were in HW equilibrium. Significant correlation existed between all sub‐scores of the MSSI and IL‐6 genotypes in females but only with three MSSI sub‐scores for males. The IL‐6 C/C genotype was significantly correlated with the neurological, general and total MSSI sub‐scores, generally twofold higher. There were no statistically significant correlations with CRP levels/polymorphisms and MSSI sub‐scores nor with IL‐6 polymorphisms. CRP levels decreased after ERT in patients with IL‐6 G/G or G/C genotypes but increased in patients with C/C ( p = 0.003). Conclusions: The prevalence of the IL‐6 C allele significantly influences MSSI, i.e. clinical severity, especially in females. This is unrelated to IL‐6 as a pro‐inflammatory marker as demonstrated by lack of correlations with CRP levels and genotypes. IL‐6 −174 polymorphic C allele may be a prognostic marker in Fabry disease, especially in females.