Haptoglobin (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 (HP(1) and HP(2)), HP complete deletion allele (HP(del)), 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 HP(del) allele because all of the polymorphisms were found in Japanese samples.
We collected 194 HP(del) heterozygotes and 385 randomly selected samples without HP(del) 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.
We 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.
We suggest that rs5472 is a strong genetic determinant of HP levels in Japanese samples, in addition to rs2000999, the common HP alleles, and HP(del). Further, the haplotypes of these polymorphisms were determined automatically and the effects of the polymorphisms were clearer in HP(del) heterozygotes than samples without HP(del).
Copyright © 2014 Elsevier B.V. All rights reserved.