Association of a Locus in theCAMTA1Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis

Common polymorphisms of chemokine (C‐X3‐C motif) receptor 1 gene modify amyotrophic lateral sclerosis outcome: A population‐based study

“…Alternatively, it is possible that the observed discrepancy between the 2 studies indicates that the association of ALS with CX3CR1 gene common polymorphism is not real. It is noteworthy that these SNPs did not show an effect on survival in ALS patients in a previous genome‐wide association study (GWAS) involving over 4,000 patients, although the large number of variants that were tested in that study resulted in a more stringent P ‐value threshold for declaring genome‐wide significance . Although this is the most likely explanation, we do not want to dismiss prematurely the survival effect of CX3CR1 functional polymorphisms because 6 months represents a substantial 20% change in survival in a disease associated with rapid progression and death.…”

“…Also, the presence of at least 1 minor allele of the rs3011225 SNP located on chromosome 1p34.1 was associated with earlier age of onset in a meta‐analysis of 13 GWAS cohorts . Finally, the presence of an intermediate CAG repeat expansion in the ATXN2 gene not only is a risk factor for ALS but also is associated with a spinal phenotype and reduces survival by 1 year …”

“…In the past few years, several studies of genetic modifiers of ALS phenotype or prognosis have been conducted. The rs12608932 CC genotype of the UNC13A gene has been demonstrated in several populations to be related to a shorter survival than the A/C and A/A genotypes . More recently, a large international meta‐analysis of GWAS found 2 loci (at 10q23, SNP rs139550538 and at 1p36, rs2412208) in which the presence of the minor alleles in the homozygous state were significantly associated with a reduction of survival of 7 and 4 months, respectively .…”

What causes amyotrophic lateral sclerosis?

“…Genetic variations have been associated with survival duration, with the best studied being variation in the UNC13A gene 60, 61 . Variation in the CAMTA1 gene has also been associated with survival 62 . Furthermore, some risk genes harbour variants that are themselves predictors of prognosis.…”

Energy metabolism in amyotrophic lateral sclerosis: assessment of body composition and energy expenditure

“…There are also some genes that modify the clinical course of ALS (Meyer et al, 2005, Fogh et al, 2016, Lopez-Lopez et al, 2014, Taylor et al, 2016. In the absence of a cure, discovery of factors that modify disease progression is critical.…”