Investigation of the -1377 polymorphism on the Apo-1/Fas promoter in systemic lupus erythematosus patients using allele-specific amplification

Pathology. 2000 May;32(2):126-30. doi: 10.1080/003130200104376.

Abstract

Apoptosis mediated by the Apo-1/Fas and Fas ligand pathways has been implicated in many disorders, including autoimmunity and tumorigenesis. The recent identification of two polymorphisms on the 5' flanking region of the human Apo-1/Fas gene has provided useful markers for investigation of the genetic contribution of the Apo-1/Fas gene in these diseases. The Mval polymorphism at the -670 nucleotide position is frequent in the normal population, with 51% heterozygosity. The other polymorphism, a result of single nucleotide G-->A substitution at the -1377 position, does not create or delete any restriction enzyme digestion sites. In this paper, we describe a simple and rapid method for detecting the -1377 polymorphism by using allele-specific amplification (ASA). Using the ASA method, the -1377 polymorphism in a normal Caucasian population was characterised. Frequencies of 0.13 and 0.87 for allele A and G, respectively, were observed and the homozygosity of the mutant allele (A) was found in only 2% of the population. We subsequently examined the -1377 polymorphism in sporadic systemic lupus erythematosus (SLE) patients (n = 86). The results showed that both genotype distribution and allele frequencies in SLE patients were similar to that in controls, suggesting that the -1377 promoter polymorphism is unlikely to be associated with SLE susceptibility. The description of this rapid detection method and characterisation of the -1377 polymorphism are useful means for future genetic studies in diseases in which the Fas-mediated apoptosis may be involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Apolipoprotein A-I / genetics*
  • DNA / analysis
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • Fas Ligand Protein
  • Female
  • Gene Amplification
  • Genotype
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Pedigree
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic*

Substances

  • Apolipoprotein A-I
  • DNA Primers
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • DNA

Associated data

  • GENBANK/X87625