Analysis of HTT CAG repeat expansion among healthy individuals and patients with chorea in Korea
Related Experiment Video
Updated: Jul 10, 2025
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Ryul Kim1, Moon-Woo Seong2, Bumjo Oh3
1Department of Neurology, Inha University Hospital, Inha University College of Medicine, Incheon, South Korea.
Insights
This study on Huntington's disease (HD) in Korea found lower frequencies of reduced penetrance and intermediate cytosine-adenine-guanine (CAG) alleles. Intermediate CAG alleles were linked to a higher chorea risk in older Koreans.
Area of Science:
- Genetics
- Neurology
- Epidemiology
Background:
- Huntington's disease (HD) epidemiology in Korea differs from Western countries, with unclear genetic disparities.
- The HTT gene's cytosine-adenine-guanine (CAG) repeat size is crucial for HD pathogenesis.
- Understanding Korean population-specific genetic variations in HD is essential.
Purpose of the Study:
- To characterize cytosine-adenine-guanine (CAG) repeat lengths in the HTT gene within the Korean population.
- To determine the clinical significance of CAG repeat sizes, including intermediate and reduced penetrance alleles, in relation to chorea development.
- To establish normative CAG repeat length data for healthy Koreans.
Main Methods:
- Analyzed HTT gene CAG repeat lengths in 941 healthy individuals and 954 patients with chorea in Korea.
- Calculated frequencies of reduced penetrance (36-39 CAG) and intermediate (27-35 CAG) alleles.
- Used logistic regression to assess the association between intermediate alleles and chorea in individuals aged ≥55 years.
Main Results:
- Mean CAG repeat length in healthy Koreans was 17.5 ± 2.0; reduced penetrance allele frequency was 0.05%, intermediate allele frequency was 0.69%.
- Confirmed HD in 213 patients with CAG repeat lengths from 39 to 140 (mean 45.2 ± 7.9).
- Intermediate CAG alleles significantly correlated with increased chorea risk in individuals ≥55 years (onset 63-84 years).
Conclusions:
- Korean population exhibits lower frequencies of reduced penetrance and intermediate CAG repeat alleles compared to Western populations.
- Intermediate CAG repeat alleles may elevate chorea risk in the elderly Korean population.
- Further large-scale studies are warranted to validate these findings and explore clinical implications.
Background:
Although the epidemiology of Huntington's disease (HD) in Korea differs notably from that in Western countries, the genetic disparities between these regions remain unclear.
Objective:
To investigate the characteristics and clinical significance of cytosine-adenine-guanine (CAG) repeat size associated with HD in the Korean population.
Methods:
We analyzed the CAG repeat lengths of the HTT gene in 941 healthy individuals (1,882 alleles) and 954 patients with chorea (1,908 alleles) from two referral hospitals in Korea. We presented normative CAG repeat length data for the Korean population and computed the reduced penetrance (36-39 CAG) and intermediate allele (27-35 CAG) frequencies in the two groups. Furthermore, we investigated the relationship between intermediate alleles and chorea development using logistic regression models in individuals aged ≥55 years.
Results:
The mean (±standard deviation) CAG repeat length in healthy individuals was 17.5 ± 2.0, with a reduced penetrance allele frequency of 0.05 % (1/1882) and intermediate allele frequency of 0.69 % (13/1882). We identified 213 patients with genetically confirmed HD whose CAG repeat length ranged from 39 to 140, with a mean of 45.2 ± 7.9 in the longer allele. Compared with normal CAG repeat alleles, intermediate CAG repeat alleles were significantly related to a higher risk of developing chorea (age of onset range, 63-84 years) in individuals aged ≥55 years.
Conclusions:
This study provides insights into the specific characteristics of CAG repeat lengths in the HTT gene in the Korean population. The reduced penetrance and intermediate allele frequencies in the Korean general population seem to be lower than those reported in Western populations. The presence of intermediate alleles may increase the risk of chorea in the Korean elderly population, which requires further large-scale investigations.
More Related Videos
08:22A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
Published on: September 16, 2019
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022