INVESTIGATION OF THE -1377 POLYMORPHISM ON THE APO-1/FAS PROMOTER IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS USING ALLELE-SPECIFIC AMPLIFICATION

Author: Huang Qi Rong   Manolios Nicholas  

Publisher: Ashgate Publishing Ltd

ISSN: 0031-3025

Source: Pathology, Vol.32, Iss.2, 2000-05, pp. : 126-130

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

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 MvaI 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.