Beyond genetic factors, the onset of Huntington’s disease later in life was linked to being in a stable partnership, living in large cities and having lower levels of education, according to a large-scale analysis.
In comparison, younger age at disease onset was associated with suicidal behavior and alcohol, drug and tobacco use.
Since psychiatric symptoms may precede motor impairment by several years, the researchers noted that “the risk of suicide should be monitored in all individuals and especially in younger patients.”
The analysis was published in the Journal of Neurologyin the study”Beyond the number of CAG triplets: exploring potential predictors of delayed age of onset in Huntington’s disease.”
Huntington’s disease is caused by an expansion of the CAG repeat in the huntingtin (HT) gene, in which C stands for cytosine, A for adenine and G for guanine – all building blocks of DNA. CAG is usually repeated 10 to 35 times in this gene, whereas people with 40 or more repeats develop Huntington’s disease.
The onset of symptoms usually occurs in the fourth or fifth decade of life, but can range from childhood to late adulthood.
CAG repeat length is the most important factor determining age of onset and accounts for about 70% of the variability in age of onset. In some cases, a CAG repeat range of 40 to 42 may be linked to a typical onset in the middle adult as well as a late onset after age 60.
What non-genetic factors have the researchers studied?
To identify non-genetic factors that may influence the age of onset of Huntington’s disease, researchers at the Università Cattolica del Sacro Cuore in Italy collected demographic, behavioral and socio-environmental data from Enroll participants. -HD, a global observational study in Huntington’s disease. disease families.
The team analyzed data from 5,053 Caucasian Europeans with a confirmed diagnosis of Huntington’s, who carry at least 36 CAG repeats. A subgroup of 593 patients who all shared 41 CAG repeats was also studied alongside a group of 630 people with absent or unknown family history.
Among all participants, the mean age of onset was 46.18 years. In this group, predictors of age of onset included number of CAG triplets, family inheritance, marital status, level of education, place of residence, suicidal behavior, abuse of alcohol, drug use and smoking habits in their medical history.
Specifically, older age of onset was related to lower number of CAG repeats, family history, lifelong and stable relationship (married or widowed), lower level of education and life in big cities. A younger age of onset was associated with suicidal behavior and the use of alcohol, drugs and tobacco.
The mean age of onset of 56.80 years in patients with 41 CAG repeats was older than the entire sample. People with older age of onset were more likely to be in a stable partnership, to have less frequent suicidal behaviors and to use and abuse drugs, and to have an unknown family history/ missing. Factors predicting early onset included heredity, singleness, and drug use. The team detected no gender differences.
Among patients with no known family history of HD, the mean age of onset was 53.78 years. Here, significant predictors of a younger onset included suicidal behaviors, depression, smoking habits, and drug use.
“There is a great variation in [age of onset] this cannot be explained by [Huntington’s] pathological mutation of the gene, and our results demonstrate that non-genetic factors could also modulate its impact,” the researchers concluded.
“These data set the stage for reasoning about determinants beyond CAG repeats that may be involved in [age of onset] and provide potentially valuable information to guide disease-modifying therapeutic strategies and future clinical trial designs,” they added.