Aim The aim of this case-control study was to investigate both the distribution of MCP-1, eNOS, tPA and PAI-1 gene polymorphism and correlation of genotypes and phenotypes. Method Between September 1997-January 2005, 20 patients with HPS (group 1) were compared with a group of cirrhotic patients (group 2, n = 19) as well as unrelated healthy controls (group 3, n = 59) in respect to MCP1, eNOS, tPA and PAI-1 gene polymorphism frequency distribution. Results MCP1-2518G allele carriage in patients with HPS was higher than in controls (P = 0.01). In non-HPS cirrhotic patients, eNOS Glu298Asp, Asp gene carriers and frequency of Asp alleles were detected to be considerably higher than in patients with HPS and healthy controls (P < 0.05). Conclusion HPS is more common in patients with MCP-1 2518G gene carriage; conversely it is less frequent in patients with high frequency of eNOS 298Asp allele and eNOS 298Asp carriage.