title: Can APOE and MTHFR polymorphisms have an influence on the severity of cardiovascular manifestations in Italian Pseudoxanthoma elasticum affected patients?
abstract: BACKGROUND
  The clinical phenotype of Pseudoxanthoma elasticum (PXE) affected patients, although progressive with age, is very heterogeneous, even in the presence of identicalABCC6mutations, thus suggesting the occurrence of modifier genes. Beside typical skin manifestations, the cardiovascular (CV) system, and especially the peripheral vasculature, is frequently and prematurely compromised.
  
  
  RESULTS
  A cohort of 119 Italian PXE patients has been characterized for apolipoprotein E (APOE) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms by PCR. The severity of the clinical phenotype has been quantified according to the Phenodex PXE International score system. Statistical analysis (chi2test, odd ratio, regression analysis, analysis of variance) were done by GraphPad. Data demonstrate that the frequency ofAPOEalleles is similar in PXE patients and in healthy subjects and that the allelic variant E2 confers a protection against the age-related increase of CV manifestations. By contrast, PXE patients are characterized by high frequency of theMTHFR-T677T polymorphism. With age, CV manifestations in T677T, but also in C677T, patients are more severe than those associated with the C677C genotype. Interestingly, compound heterozygosity for C677T and A1298C polymorphisms is present in 70% of PXE patients.
  
  
  CONCLUSIONS
  PXE patients may be screened for these polymorphisms in order to support clinicians for a better management of disease-associated CV complications.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Boraldi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Costa
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rabacchi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ciani
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Vanakker
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Quaglino
keywords: APOE, apolipoprotein E; Apolipoprotein E; CV, cardiovascular; Cardiovascular; HDL, high density lipoproteins; Hcy, homocysteine; MTHFR, methylenetetrahydrofolate reductase; Methylenetetrahydrofolate reductase; PXE, Pseudoxanthoma elasticum; Pseudoxanthoma elasticum; Skin-disease