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

Apoptosis mediated by the Apo-1/Fas and Fas ligand pathways has been implic ated in many disorders, including autoimmunity and tumorigenesis. The recen t identification of two polymorphisms on the 5' flanking region of the huma n Apo-1/Fas gene has provided useful markers for investigation of the genet ic contribution of the Apo-1/Fas gene in these diseases. The Mval polymorph ism at the -670 nucleotide position is frequent in the normal population, w ith 51% heterozygosity. The other polymorphism, a result of single nucleoti de G --> A substitution at the -1377 position, does not create or delete an y restriction enzyme digestion sites. In this paper, we describe a simple a nd rapid method for detecting the -1377 polymorphism by using allele-specif ic amplification (ASA). Using the ASA method, the -1377 polymorphism in a n ormal 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 (S LE) patients (n = 86). The results showed that both genotype distribution a nd allele frequencies in SLE patients were similar to that in controls, sug gesting that the -1377 promoter polymorphism is unlikely to be associated w ith SLE susceptibility. The description of this rapid detection method and characterisation of the -1377 polymorphism are useful means for future gene tic studies in diseases in which the Fas-mediated apoptosis may be involved .