Negative resultsLack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis
Introduction
Several studies have suggested a compromised DNA repair in amyotrophic lateral sclerosis (ALS), and a role for the apurinic/apyrimidinic endonuclease 1 (APEX1) in disease onset and progression is still debated. APEX1 removes the abasic site generated by the action of DNA glycosylases after the removal of a damaged base (Fishel et al., 2007). In 1997 the frontal cortical levels and the activity of APEX1 were determined in ALS patients and controls, and found to be significantly reduced in the first group (Kisby et al., 1997). However, a few years later, others observed an increased APEX1 activity in ALS brain and spinal cord motor neurons, suggesting that this enzyme is active and competent in ALS tissues (Shaikh and Martin, 2002). A common polymorphism resulting in an Asp148Glu amino-acidic change in APEX1 that alters the repair activity was suggested to be associated with an increased sALS risk in a Scottish cohort of 117 sporadic ALS (sALS) patients and 58 controls (Hayward et al., 1999). To further address the role of the APEX1 Asp148Glu polymorphism in sALS pathogenesis we screened an Italian cohort of 134 sALS patients (94 males and 40 females, mean age 65.1 ± 10.9 years, range 33–85) and 129 matched controls (88 males and 41 females, mean age 62.9 ± 15.4 years, range 32–83) for the presence of the APEX1 Asp148Glu polymorphism, and searched for association between the polymorphism and both sALS risk and clinical presentation, including age and site of onset and disease progression.
Section snippets
Materials and methods
Genotyping was performed by PCR/RFLP techniques; primers and protocols were derived from literature (Zhang et al., 2005; Li et al., 2006).
Results
Table 1 shows the genotype distributions and the allele frequencies of the APEX1 Asp148Glu polymorphism in sALS patients and controls. There was no statistically significant difference in allele frequencies between sALS cases and controls (P = 0.975). No statistically significant difference was observed in genotype distributions between sALS cases and controls, even when data were stratified by gender (Table 1). The results of the association between the APEX1 Asp148Glu polymorphism and the
Discussion
In the present study no difference in APEX1 Asp148Glu allele and genotype frequencies was found between sALS patients and controls, nor was the polymorphism associated with age or site of onset, or duration of the disease. Present results suggest that, at least in the Italian population, the APEX1 Asp148Glu polymorphism does not contribute to sALS pathogenesis. At best of our knowledge, the present is the first study which evaluate the contribution of the APEX1 Asp148Glu polymorphism on sALS