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Genetics
C04 The effects of GRIN gene variations on age at onset of Turkish Huntington's disease patients
  1. N E Tunali1,
  2. A Acar-Hazer1,
  3. N Erginel-Unaltuna2,
  4. H A Hanagasi3
  1. 1Halic University, Istanbul, Turkey
  2. 2Istanbul University, Istanbul, Turkey
  3. 3Istanbul Faculty of Medicine, Istanbul, Turkey

Abstract

Background The length of the CAG repeats is the major determinant in defining the 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 N-methyl-D-aspartate glutamate receptors (GRIN: glutamate receptor, ionotropic) have been proposed as important putative modifiers since glutamate mediates fast excitatory neurotransmission in the brain.

Aim We aimed to analyse the association between GRIN1 (rs6293), GRIN2A (rs1969060) and GRIN2B (rs1806201, rs890) polymorphisms and AO of Turkish HD patients.

Methods DNA samples of 102 unrelated HD patients and 102 healthy age and sex matched controls were genotyped. GRIN genotyping was performed with RFLP analysis. Hardy–Weinberg test statistics was computed for each SNP. The odds ratios and independent sample t tests for genotypes were computed for association of genotypes with AO.

Results According to our findings, expanded CAG repeat size explains 41.8% of the variance in AO which is in accordance with the results from other populations. However, when the entire observed CAG repeat sizes are considered, the remaining variance could not be attributed to any of the studied SNPs. Classification of SNP genotypes into four CAG repeat length intervals did not reveal any important findings either, except GRIN1 rs6293 in the >50 CAG repeats group (p=0.016). Also, there is a significant association of this SNP to HD (p=0.015) and the GG genotype constitutes a risk factor (OR=2663).

Conclusions rs6293 SNP can be regarded as an AO modifier for Turkish HD patients only with 50 or higher CAG repeats in their IT15 gene and the GG genotype constitutes a risk factor for Turkish HD patients. Supplemental studies are needed to confirm GRIN genes as genetic modifiers of AO in HD.

  • age at onset
  • NMDAR
  • GRIN

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