by Researchers have identified a new genetic variant that may influence survival among sporadic amyotrophic lateral sclerosis (ALS) patients in Japan.
A genetic study of more than 1,000 ALS patients found that small changes in the FGF1, THSD7A, and LRP1 Genetics can affect a patient’s prognosis. In the nerve cells taken from the patient, the identified changes lead to low gene activity and reduced cell survival.
“The identification of genetic factors associated with the survival of patients with ALS and the development of cellular models from the patient expressing these factors may contribute to the development of targeted therapies for ALS,” the researcher wrote.
Lesson, “Genetic factors affecting survival in Japanese patients with sporadic amyotrophic lateral sclerosis: a genome-wide association study and validation in iPSC-derived motor neurons from patients.,” was published in Journal of Neurology, Neurosurgery & Psychiatry.
Mutations in more than 40 genes have been linked to familial ALS, or familial ALS. On the other hand, in many cases of sporadic ALS, or those with no known family history, the disease-causing mutation has not been identified.
However, research shows that small genetic variations, called single nucleotide polymorphisms (SNPs), can affect the prognosis and survival of these patients.
Genetic factors in Asian patients have not been identified, scientists say
SNPs refer to genetic changes that affect only one nucleotide, or block of DNA. They are the most common type of genetic variation found in humans, including healthy people. While they do not directly cause disease themselves, they can affect disease risk, disease presentation, or diagnosis.
Most studies examining SNPs linked to ALS prognosis have been conducted in white people, so genetic factors affecting survival among Asian patients have not been identified, according to the scientists.
In the study, the Japan Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS) study group, which includes researchers from several Japanese institutions, conducted a genome-wide association study (GWAS) to search for genetic contributors to survival among 1,076 patients with rare ALS. Japan.
GWAS studies examine a large number of genes – in a large number of patients – looking for a relationship between a SNP and the outcome of interest, in this case survival.
Finally, they identified SNPs in three specific genes- FGF1, THSD7A, and LRP1 – which have been significantly associated with survival outcomes in ALS patients.
Variations in other genes, such as CAMTA1 or IDEA, which have previously been found to influence survival in white patients, were not associated with survival in the Japanese population.
“Genetic factors affecting the prognosis of Japanese patients with ALS may differ from those of Caucasian patients with ALS,” the researchers wrote.
To learn more about the effects of these SNPs, the researchers cloned nerve cells from programmed blood cells isolated from patients with different types.
Certain SNPs associated with reduced gene activity
In these motor neurons, the nerve cells damaged in ALS, they found that there are certain SNPs FGF1 and THSD7A they are associated with reduced gene activity, and reduced cell survival.
Genetic modification to reduce FGF1 or THSD7A in nerve cells from healthy adults similarly led to cell death and decreased survival.
FGF1 It is a gene involved in the growth and development of nerve cells. Genetic mutations have previously been linked to a range of neurological diseases. Because the SNP identified in this study appears to be decreasing FGF1 activity and adversely affect survival, “FGF1 may have a positive effect on the survival of patients with ALS and may be a therapeutic target to improve prognosis,” the researchers wrote.
The potential role of THSD7A in ALS is less clear, according to the team, which said “further research is warranted.”
Ultimately, the scientists believe that their findings will contribute to the development of better treatments for ALS patients.
“Because of the diversity of patients with rare ALS, it is necessary to develop a personalized medicine program,” the researchers wrote.
They added that the use of patient-derived nerve cells to more closely study genetic variants identified in GWAS studies “could serve as a successful model for the development of personalized medicine for patients with ALS.”
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