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Meta-Analysis
. 2019 Jul:494:138-142.
doi: 10.1016/j.cca.2019.03.1617. Epub 2019 Mar 18.

Genetic determinants of circulating haptoglobin concentration

Nabila Kazmi  1 , Yoshiro Koda  2 , Ndeye Coumba Ndiaye  3 , Sophie Visvikis-Siest  3 , Matthew J Morton  4 , Tom R Gaunt  1 , Ian Galea  5
Affiliations
Meta-Analysis

Genetic determinants of circulating haptoglobin concentration

Nabila Kazmi et al. Clin Chim Acta. 2019 Jul.

Abstract

Haptoglobin (Hp) is a major plasma acute-phase glycoprotein, which binds free haemoglobin to neutralize its toxicity. The HP gene exists as two copy number variants (CNV), Hp1 and HP2, which differ in two ways: serum Hp level and functional differences in Hp protein products. Both mechanisms may underlie the HP CNV's influence on susceptibility and/or outcome in several diseases. A single nucleotide polymorphism rs2000999 has also been associated with serum Hp level. In a meta-analysis of three studies from England, France and Japan, with a combined sample size of 1210 participants, we show that rs2000999's effect on circulating Hp level is independent from that of the HP CNV. The combined use of rs2000999 and the HP CNV can be an important genetic epidemiological tool to discriminate between the two potential mechanisms underlying differences between HP1 and HP2 alleles.

Keywords: ALSPAC; Copy number variant; Haptoglobin.

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Figures

Fig. 1
Fig. 1
Effect of the HPCNV and rs2000999 on circulating Hp level in multivariate analyses. CNV was included in the model as a dependent variable and rs2000999 as a covariate whereas gender was included as an interaction term. The labels indicate the comparison being made; for instance CNV:HP2 indicates the change in Hp level in g/L for every HP2 allele (i.e. the beta coefficient). Gender:M = the gender is male.
Fig. 2
Fig. 2
Effect of HP-CNV and rs2000999 on circulating Hp level in univariate analyses.
See this image and copyright information in PMC

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