engleski

Polymorphism of ApoE, MTHFR and PON1 gene in Alzheimer disease

Although the association of some genetic and environmental factors with the genesis of Alzheimer disease (AD) has been suggested, the etiology of AD has not been fully clarified to date. A strong association has been proposed for APOE gene, i.e. its epsilon 4 (e4) allele, and development of AD. Currently, inflammatory reactions are considered to be a major factor involved in the pathogenesis of AD. This hypothesis is supported by neurotoxicity of inflammatory reactions products. PON1 as part of HDL complex has been implicated in organophosphate detoxification and LDL protection from peroxidation. Genotype distribution and allele frequencies of APOE, MTHFR, and PON1 were investigated by PCR-RFLP using restriction enzyme CfoI, Hinf I, and Alw I, respectively, in the group of AD patients (n=50) and healthy control (n=187). Study results revealed 35,7 % of AD patients and only 3.8% of controls to be carriers of APOE e4 allele. A significant difference of APOE e4 allele (p<0.001, X2-test) and genotype distribution (p<0.001, X2-test) was found between AD and control groups. The MTHFR genotype distribution also showed a significant difference (p=0.037) between the control and AD group, however, although MTHFR (+) allele frequency was higher in AD group, the difference was not significant (p=0.275). There were no significant differences in PON1 genotype distribution or allele frequency between the groups either. However, AD patients with e4/e4 genotype had a significantly different allele (p=0.011) and genotype distribution (p<0.001) of MTHFR gene from both the control and AD patient group as whole. Concerning PON1 gene, comparison of AD e4/e4 patients with controls and AD patients as a whole, indicated a significant difference of genotype distribution (p=0.024) only. Although obtained in a small study group, these preliminary results suggest that MTHFR and PON1 could be associated with the development of AD. Studies in a larger of patient groups are obviously required.

Alzheimer disease; ApoE; MTHFR; PON1

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