Description

The length of the CAG repeat tract is the major determinant of age of onset (AO) of Huntington’s Disease (HD) However, there remains a significant variance in AO when the expanded repeat size is ruled out. The search for genetic modifiers has revealed various candidate loci; however, many reports have been contradictory. The N-methyl-d-aspartate receptors (NMDAR) have been proposed as an important putative modifier. We aimed to determine whether polymorphisms in NMDAR-coding genes have an effect on the AO. We analyzed the association between GRIN1 (rs6293), GRIN2A (rs1969060), and GRIN2B (rs1806201, rs890) polymorphisms and AO of Turkish HD patients. According to our findings, expanded CAG repeat size explains 41.8% of the variance in AO. Upon classification of genotypes into CAG repeat length intervals, rs6293 can be considered as an AO modifier for Turkish HD patients with 50 or higher CAG repeats. In addition to that, we found a significant association of this polymorphism to HD, with the GG genotype constituting a risk factor. Candidate genetic modifiers should be tested in different populations since their effects may exist only in groups of specific ethnic origins. Defining such modifiers will help in complete understanding of HD pathogenesis and in designing therapeutic targets.

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