Glyoxalase I A111E, paraoxonase 1 Q192R and L55M polymorphisms in Italian patients with sporadic cerebral cavernous malformations: A pilot study

C. Rinaldi, P. Bramanti, A. Famà, C. Scimone, L. Donato, C. Antognelli, C. Alafaci, F. Tomasello, R. D'Angelo, A. Sidoti

Research output: Contribution to journalArticle

Abstract

It is already known that the conditions of increased oxidative stress are associated to a greater susceptibility to vascular malformations including cerebral cavernous malformations (CCMs). These are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1(Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Polymorphisms in the genes encoding for enzymes involved in the antioxidant systems such as glyoxalase I (GLO I) and paraoxonase I (PON I) could influence individual susceptibility to the vascular malformations. A single nucleotide polymorphism was identified in the exon 4 of GLO 1 gene that causes an amino acid substitution of Ala for Glu (Ala111Glu). Two common polymorphisms have been described in the coding region of PON1, which lead to glutamine → arginine substitution at 192 (Q192R) and a leucine → methionine substitution at 55 (L55M). The polymorphisms were characterized in 59 patients without mutations in the CCM genes versus 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that the frequency of patients carrying the GLO1 A/E genotype among the case group (56%) was four-fold higher than among the controls (14.1%). In the cohort of CCM patients, an increase in the frequency of PON192 Q/R genotype was observed (39% in the CCM group versus 3.7% in the healthy controls). Similarly, an increase was observed in the proportion of individuals with the genotype R/R in the disease group (5%) in respect to the normal healthy cohort (0.5%). Finally, the frequency of the PON55 heterozygotes L/M genotype was 29% in patients with CCMs and 4% in the healthy controls. The same trend was observed in PON55 homozygous M/M genotype frequency (CCMs 20% vs controls 10%). The present study aimed to investigate the possible association of GLO1 A111E, PON1 Q192R and L55M polymorphisms with the risk of CCMs. We found that individuals with the GLO1 A/E genotype, PON192/QR-RR genotypes and PON55/LM-MM genotypes had a significantly higher risk of CCMs compared with the other genotypes. However, because CCM is a heterogeneous disease, other additional factors might be involved in the initiation and progression of CCM disease.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalJournal of Biological Regulators and Homeostatic Agents
Volume29
Issue number2
Publication statusPublished - Apr 1 2015

Keywords

  • Cerebral cavernous malformation
  • Glyoxalase I
  • Paraoxonase I

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Cancer Research
  • Immunology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Immunology and Allergy

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    Rinaldi, C., Bramanti, P., Famà, A., Scimone, C., Donato, L., Antognelli, C., Alafaci, C., Tomasello, F., D'Angelo, R., & Sidoti, A. (2015). Glyoxalase I A111E, paraoxonase 1 Q192R and L55M polymorphisms in Italian patients with sporadic cerebral cavernous malformations: A pilot study. Journal of Biological Regulators and Homeostatic Agents, 29(2), 153-159.