Genetic factors associated with serum haptoglobin level in a Japanese population

Abstract

BackgroundHaptoglobin (HP) is an acute-phase protein induced by inflammatory stimuli. Its serum level varies in several clinical conditions and among individuals. The common HP alleles (HP1 and HP2), HP complete deletion allele (HPdel), and two SNPs (rs5472 and rs2000999) have been reported to be possible genetic determinants of serum HP levels so far. However, no studies have explored the relationship among the polymorphisms using the same samples. For this purpose, the impact of these polymorphisms was examined using Japanese heterozygote samples of the HPdel allele because all of the polymorphisms were found in Japanese samples. MethodsWe collected 194 HPdel heterozygotes and 385 randomly selected samples without HPdel from 5679 Japanese samples. Genotyping of all polymorphisms was performed by PCR using hydrolysis probes. Phenotyping of the common HP alleles was determined by polyacrylamide gel electrophoresis. Serum HP level was measured by a sandwich ELISA. ResultsWe observed a significant association between each of the polymorphisms and serum HP level. Two SNPs, rs5472 and rs2000999, were found to be in almost absolute linkage disequilibrium. ConclusionsWe suggest that rs5472 is a strong genetic determinant of HP levels in Japanese samples, in addition to rs2000999, the common HP alleles, and HPdel. Further, the haplotypes of these polymorphisms were determined automatically and the effects of the polymorphisms were clearer in HPdel heterozygotes than samples without HPdel.