HD Lighthouse Contributing Editor's Comment: Although CAG counts are highly correlated with age of onset (the higher the count, the earlier the average age of onset), there is considerable variation in ages of onset between individuals with the same CAG count. Studies with thousands of people in Venezuela have suggested that other genes and environmental factors also influence age of onset.

Researchers are looking for these other genes with the idea that they might point the way to an effective treatment.
--Marsha Miller
Posted to the HDL: 15 Jan 2005

Modulation of age at onset of Huntington disease patients by variations in TP53 and human caspase activated DNase (hCAD) genes.

Variation of age at onset (AO) in Huntington's disease (HD) cannot be explained by the number of CAG repeats alone in the mutant alleles of the gene huntingtin (Htt). Given the ability of expanded polyglutamine (poly-Q) tract present in Htt protein to interact with other proteins and increased neuronal cell death by apoptosis, variations in the genes coding for htt-interacting proteins and those involved in apoptosis are likely to alter the AO in HD. In the present investigation, we studied two single nucleotide polymorphisms (SNPs), namely, R72P in TP53 gene coding for transcription factor p53, which interacts with Htt protein and R196K in human caspase activated DNase (hCAD) gene involved in apoptosis to investigate their role as genetic modifiers of the AO of HD. Multiple linear regression analysis revealed that variations in TP53 and hCAD genes explained 12.6% and 6%, respectively, of the variance in the AO of HD after accounting for the effect of expanded CAG repeats. Statistical analysis further showed a significant effect of the interaction term between expanded CAG repeats and variations at each of TP53 and hCAD genes upon the AO. This data demonstrated that variations in TP53 and hCAD genes modulate the AO of HD.

Tracked on the Lighthouse:
age of onset
apoptosis
P53

# # #

Source: Neurosci Lett. 2005 Feb 10;374(2):81-6

printer friendly version

 

	Read the HDAC/HDLighthouse Forum. Post your comments