DETECTION OF 2 NEW POLYMORPHISMS BY PCR-SSCP ANALYSIS OF THE HISTIDINE-RICH GLYCOPROTEIN GENE IN 3 FAMILIES WITH ABNORMAL PLASMA HRG LEVELS

Objective: Search for mutations in the histidine-rich glycoprotein (HR G) gene that might explain the abnormal HRG levels in members of three families. Subjects and methods: PCR-SSCP was used to screen the HRG g ene in two families with high HRG levels and one HRG-deficient family. Results: We detected two new single base-pair substitutions. A substi tution from A to G was found in the promoter region at position -112 a nd a substitution from C to T was found in intron 1, at 12 base-pairs downstream of exon 1. The population frequencies of the rare alleles G and T are 2% and 10%, respectively. Both substitutions have frequenci es higher than 1% and should be considered as polymorphisms. Conclusio n: No cosegregation between HRG levels and the single base-pair substi tutions was observed, indicating that both polymorphisms have no effec t on HRG plasma levels in these families. The abnormal HRG levels in t he families could partly be explained by a previously described prolin e-serine polymorphism (P186S) which is reported to account for 59% of the variation in HRG plasma levels.