Detection of two new polymorphisms by PCR-SSCP analysis of the histidine-rich glycoprotein gene in three families with abnormal plasma HRG levels

Abstract

Summary Objective: Search for mutations in the histidine-rich glycoprotein (HRG) gene that might explain the abnormal HRG levels in members of three families. Subjects and methods: PCR-SSCP was used to screen the HRG gene in two families with high HRG levels and one HRG-deficient family. Results: We detected two new single base-pair substitutions. A substitution from A to G was found in the promoter region at position −112 and 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 frequencies higher than 1% and should be considered as polymorphisms. Conclusion: No cosegregation between HRG levels and the single base-pair substitutions was observed, indicating that both polymorphisms have no effect on HRG plasma levels in these families. The abnormal HRG levels in the families could partly be explained by a previously described proline-serine polymorphism (P186S) which is reported to account for 59% of the variation in HRG plasma levels.