Key result
FAS rs2234978 and CASP8 rs1045487 minor alleles are strongly linked to probable ALPS.
Why the study?
Patients who fulfill ALPS diagnostic criteria without identified disease-causing mutations are classified as ALPS phenotype, comprising about one third of all patients, and the genetic basis in these cases is unclear.
Case-Control (n=125)
No
Odds Ratio: 0.0188 (95% CI 0.0068–0.0517)
Absolute Event Rate: 92% vs 27%
p-value: p=0.001
Polymorphisms in the FAS (rs2234978) and CASP8 (rs1045487) genes may contribute to the susceptibility of developing the ALPS phenotype in patients without known pathogenic mutations.
These SNPs may contribute to ALPS susceptibility; hypothesis-generating and should not yet change clinical evaluation.
Defects in genes that have role in apoptotic pathways result in development of Autoimmune Lymphoproliferative Syndrome (ALPS) and ALPS related disorders. Germline and somatic FAS mutations, FASL and CASP10 mutations constitute other genetic defects in ALPS. Patients who fulfill ALPS diagnostic criteria and do not have any identified known disease causing mutations are classified as ALPS-unknown or ALPS phenotype and comprise about one third of all patients. CASP8, NRAS and KRAS gene mutations were reported for ALPS related diseases. We performed DNA sequence analysis in 25 unrelated patients with probable ALPS for FAS, FASL and CASP8 gene defects. Pathogenic mutations could not be found in the FAS, FASL and CASP8 genes. However, we found that the frequencies of SNPs rs2234978 and rs1045487 of FAS and CASP8 genes were significantly higher in the patients. Our results suggest that CASP8 and FAS gene polymorphisms in particular, may contribute to the susceptibility to development of ALPS phenotype.
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Tan et al. (2015) conducted a case-control in Autoimmune Lymphoproliferative Syndrome (ALPS) phenotype (n=125). FAS (rs2234978) and CASP8 (rs1045487) gene polymorphisms vs. Healthy controls was evaluated on Frequency of FAS SNP rs2234978 minor allele T (OR 0.0188, 95% CI 0.0068-0.0517, p=0.001). FAS SNP rs2234978 and CASP8 SNP rs1045487 minor allele frequencies were significantly higher in patients with probable ALPS compared to healthy controls.
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