Genotype-phenotype correlations in a chinese population with familial amyotrophic lateral sclerosis

Objective To investigate whether GSTA1, GSTO2, and GSTZ1 are relevant to an increased risk of amyotrophic lateral sclerosis (ALS) in a Chinese population. Methods In this study, 143 sporadic ALS (sALS) patients (83 men, 60 women) and 210 age- and sex-matched healthy subjects were enrolled. Blood samples were collected by venipuncture. Genomic DNA was isolated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) according to the manufacturer’s instructions. The potential associations between ALS and GSTA1, GSTO2, and GSTZ1 polymorphisms were estimated using chi-squared analysis and unconditional logistic regression. Results The D allele and genotype frequencies of GSTO2 were increased in sALS patients compared with healthy subjects, indicating that the GSTO2 DD genotype was associated with an increased risk of sALS (odds ratio [OR] = 3.294, 95% confidence interval [CI] = 1.039–10.448). However, a significant association between the DD genotype and the risk of sALS was evident in men only (OR = 7.167, 95% CI = 1.381–37.202). Conclusion This study revealed that the D allele and genotype frequencies of GSTO2 were increased in sALS patients. The GSTO2 DD genotype was associated with an increased risk of sALS in men in a Chinese population.

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389. Engineered microRNAs Against a C9ORF72 Transgenic Mouse Model To Treat Human Familial Amyotrophic Lateral Sclerosis (FALS)

Molecular Therapy ◽

10.1016/s1525-0016(16)35402-8 ◽

2014 ◽

Vol 22 ◽

pp. S148

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Mouse Model ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Familial Amyotrophic Lateral Sclerosis ◽

Lateral Sclerosis

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The densitometric physical fractionator for counting neuronal populations: application to a mouse model of familial amyotrophic lateral sclerosis

Journal of Neuroscience Methods ◽

10.1016/s0165-0270(03)00201-2 ◽

2003 ◽

Vol 129 (1) ◽

pp. 61-71 ◽

Cited By ~ 9

Author(s):

Giuseppe Luca Ciavarro ◽

Novella Calvaresi ◽

Andrea Botturi ◽

Caterina Bendotti ◽

Giuseppe Andreoni ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Mouse Model ◽

Familial Amyotrophic Lateral Sclerosis ◽

Neuronal Populations ◽

Lateral Sclerosis

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Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers

Brain ◽

10.1093/brain/awu249 ◽

2014 ◽

Vol 137 (11) ◽

pp. 2938-2950 ◽

Cited By ~ 49

Author(s):

Axel Freischmidt ◽

Kathrin Müller ◽

Lisa Zondler ◽

Patrick Weydt ◽

Alexander E. Volk ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Expression Profiles ◽

Consensus Sequence ◽

Disease Onset ◽

Therapeutic Targets ◽

Familial Amyotrophic Lateral Sclerosis ◽

Sequence Motif ◽

Mutation Carriers ◽

Disease Modifying ◽

Lateral Sclerosis

Abstract Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.

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