Aim: To screen the genetic regions of SOCS1 and SOCS3 for variations (mutations and polymorphisms). To genotype 176 individuals for the found mutations/polymorphisms and to calculate the allele frequencies and haplotypes. To establish robust genotyping assays for polymorphisms with a minor allele frequency of at least 1% for a further larger study in the Swiss HIV cohort study (SHCS).
Methods: Screening for mutations has been carried out with denaturing high pressure liquid chromatography (dHPLC) and Sanger sequencing. Genotyping assays are based on four different methods: high resolution melting (HRM) without probes, HRM with unlabelled probes, allele specific amplification (ASA) and fluorescent resonance energy transfer (FRET) probe analysis. Statistical analysis was done using Excel and HaploView.
Results: 8 mutations/polymorphisms were found in the screening experiment for SOCS1, 7 mutations/polymorphisms were found in SOCS3. Genotyping showed 7 polymorphisms in SOCS1 and 6 polymorphisms in SOCS3 which had a minor allele frequency (MAF) of at least 1%. All polymorphisms are in the 5’ or the 3’ region of the genes. No polymorphisms or mutations were found in the coding sequence.
Conclusion: In the examined Swiss population different polymorphisms were identified. Some of these single nucleotide polymorphisms (SNP) are known to be functional and modify gene expression. The established assays allow now to investigate associations of these SNPs in SOCS1 and 3 and of their haplotypes with different acute and chronic infectious and inflammatory diseases.