| Autor: |
Tourtourikov I; Department of Medical Chemistry and Biochemistry, Medical University of Sofia, 1431 Sofia, Bulgaria.; Genetic Medico Diagnostic Laboratory Genica, 1612 Sofia, Bulgaria., Dabchev K; Genetic Medico Diagnostic Laboratory Genica, 1612 Sofia, Bulgaria.; Faculty of Biology, Sofia University St. Kliment Ohridski, 1504 Sofia, Bulgaria., Todorov T; Genetic Medico Diagnostic Laboratory Genica, 1612 Sofia, Bulgaria., Angelov T; Department of Neurology, Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria., Chamova T; Department of Neurology, Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria., Tournev I; Department of Neurology, Clinic of Nervous Diseases, Medical University of Sofia, UMBAL Aleksandrovska, 1431 Sofia, Bulgaria.; Department of Cognitive Science and Psychology, New Bulgarian University, 1618 Sofia, Bulgaria., Kadiyska T; Genetic Medico Diagnostic Laboratory Genica, 1612 Sofia, Bulgaria.; Department of Physiology and Pathophysiology, Medical University of Sofia, 1431 Sofia, Bulgaria., Mitev V; Department of Medical Chemistry and Biochemistry, Medical University of Sofia, 1431 Sofia, Bulgaria., Todorova A; Department of Medical Chemistry and Biochemistry, Medical University of Sofia, 1431 Sofia, Bulgaria.; Genetic Medico Diagnostic Laboratory Genica, 1612 Sofia, Bulgaria. |
| Abstrakt: |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by wide clinical and biological heterogeneity, with a large proportion of ALS patients also exhibiting frontotemporal dementia (FTD) spectrum symptoms. This project aimed to characterize risk subtypes of the H1 haplotype within the MAPT (microtubule-associated protein tau) gene, according to their possible effect as a risk factor and as a modifying factor in relation to the age of disease onset. One hundred patients from Bulgaria with sporadic ALS were genotyped for the variants rs1467967, rs242557, rs1800547, rs3785883, rs2471738, and rs7521. Haploview 4.2 and SHEsisPlus were used to reconstruct haplotype frequencies using genotyping data from the 1000 Genomes project as controls. Genotype-phenotype correlation was investigated in the context of age of disease onset and risk of disease development. While the individual variants of the subtypes do not influence the age of onset of the disease, a correlation was found between the specific haplotype GGAGCA (H1b) and the risk of developing sALS, with results showing that individuals harboring this haplotype have a nearly two-fold increased risk of developing sALS compared to other H1 subtypes. The results from this study suggest that fine transcriptional regulation at the MAPT locus can influence the risk of ALS. |
