Effect of the 50 bp deletion polymorphism in the SOD1 promoter on SOD1 mRNA levels in Italian ALS patients

J Neurol Sci. 2012 Feb 15;313(1-2):75-8. doi: 10.1016/j.jns.2011.09.026. Epub 2011 Oct 18.

Abstract

The genetic association between homozygosity for a 50 bp deletion polymorphism in the SOD1 promoter, 1684 bp upstream of the ATG, and an increased age of symptom onset was observed in various populations of ALS patients. Moreover, it has been demonstrated that this deletion reduces SOD1 expression in vitro. The objective of the present study was to test whether the observed association is replicated in patients from an Italian population and to check whether the deletion correlates with reduced SOD1 mRNA expression in vivo. Genomic DNA from 235 Italian SALS cases and 245 age- and sex-matched donors from the same ethnic background was screened for the 50 bp SOD1 promoter deletion by real time PCR assays. No differences were observed between ALS patients and controls for the frequency of both the alleles (D=deleted, N=non-deleted; p=0.95) and genotypes (p=0.90). Furthermore, stratification of the ALS samples showed that this variation was not associated with increased age of onset in ND and DD patients in comparison to NN patients (p=0.48). Finally, we performed real-time RT-PCR to quantify SOD1 mRNA levels in 48 patients and we did not find a relevant difference among the three sub-groups of genotypes (p=0.30). Our data suggest that the studied polymorphism does not modulate SOD1 mRNA level and disease phenotype in an Italian population.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / epidemiology
  • Amyotrophic Lateral Sclerosis / genetics*
  • Base Sequence
  • Female
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics*
  • Sequence Deletion / genetics*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1
  • Young Adult

Substances

  • RNA, Messenger
  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1