Genetic variation in the myeloperoxidase gene and cognitive impairment in Multiple Sclerosis
© Manna et al; licensee BioMed Central Ltd. 2006
Received: 10 November 2005
Accepted: 27 February 2006
Published: 27 February 2006
There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to β-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS.
Genotypes and allele frequencies of the MPO polymorphism
Preserved N = 204
Impaired N = 261
Genomic DNA was prepared from leukocytes harvested from whole blood using standard methods. The PCR-RFLP based assay was used to characterise the wild-type (G) and variant (A) MPO alleles at position -463 . Statistical analyses were performed with Statistical Package for Social Sciences software SPSS (version 12.0, Chicago, IL, USA) for Windows '98/'00. In our sample of consecutive patients affected by MS, we found the cognitive deterioration was present at different degrees of severity in the majority of the patients. More in detail, two-hundred and four patients (44%) were found to be cognitively preserved by the neuropsychological evaluation, whereas 261 (56%) failed at least one test and were therefore considered cognitively impaired. The cognitively impaired group differed from the preserved group in the following characteristics: a longer disease duration, a high EDSS score, a greater proportion of individuals with secondary progressive form and a lower education. No difference was found in the number of failed neuropsychological test among subjects with different polymorphic variants (p = 0.805; Kruskal-Wallis test). No significant difference was found in the genotypic (p = 0.649; Pearson χ2-test) or allelic distribution (p = 0.517; Pearson χ2-test) of the -463 G/A promoter polymorphism of the MPO gene between preserved and impaired subjects (Table). Furthermore, considering a power of 80% and a significance level of 0.05, the power calculation for the A allele shows that the ORs detectable as significant resulted lower than 0.618 and higher than 1.527. These results suggest that the -463 G/A promoter polymorphism of the MPO gene does not confer a risk of cognitive impairment in patients with MS.
List of abbreviations
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