ArticleBlood2014
Epistasis between the haptoglobin common variant and α+thalassemia influences risk of severe malaria in Kenyan children.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Exploring the protective effects of thalassemia against malaria in Africa: a systematic review.Systematic reviews · 2026Pooled it
- Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis.Scientific reports · 2018Trial
- Kinetics of antimalarial antibodies in children with common haemoglobinopathies in a Tanzanian population.Frontiers in immunology · 2026Article
- Coinheritance of polymorphic alleles ofOne health (Amsterdam, Netherlands) · 2025Article
- ApoE: A new piece to the severe malaria puzzle.Pediatric research · 2024Article
- Haptoglobin gene diversity and incidence of uncomplicated malaria among children in Iganga, Uganda.Malaria journal · 2020Article
- Haplotype heterogeneity and low linkage disequilibrium reduce reliable prediction of genotypes for the ‑αWellcome open research · 2020Article
- Genome-wide association studies of severe P. falciparum malaria susceptibility: progress, pitfalls and prospects.BMC medical genomics · 2019Review
- Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study.The Lancet. Haematology · 2018Article
- Two complement receptor one alleles have opposing associations with cerebral malaria and interact with αeLife · 2018Article
- Haematological and electrophoretic characterisation of β-thalassaemia in Yunnan province of Southwestern China.BMJ open · 2017Article
- Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin.Cellular and molecular life sciences : CMLS · 2017Review
- Negative Epistasis between Sickle and Foetal Haemoglobin Suggests a Reduction in Protection against Malaria.PloS one · 2015Article
- Reappraisal of known malaria resistance loci in a large multicenter study.Nature genetics · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Haptoglobin (Hp) scavenges free hemoglobin following malaria-induced hemolysis. Few studies have investigated the relationship between the common Hp variants and the risk of severe malaria, and their results are inconclusive. We conducted a case-control study of 996 children with severe Plasmodium falciparum malaria and 1220 community controls and genotyped for Hp, hemoglobin (Hb) S heterozygotes, and α(+)thalassemia. Hb S heterozygotes and α(+)thalassemia homozygotes were protected from severe malaria (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.07-0.18 and OR, 0.69; 95% CI, 0.53-0.91, respectively). The risk of severe malaria also varied by Hp genotype: Hp2-1 was associated with the greatest protection against severe malaria and Hp2-2 with the greatest risk. Meta-analysis of the current and published studies suggests that Hp2-2 is associated with increased risk of severe malaria compared with Hp2-1. We found a significant interaction between Hp genotype and α(+)thalassemia in predicting risk of severe malaria: Hp2-1 in combination with heterozygous or homozygous α(+)thalassemia was associated with protection from severe malaria (OR, 0.73; 95% CI, 0.54-0.99 and OR, 0.48; 95% CI, 0.32-0.73, respectively), but α(+)thalassemia in combination with Hp2-2 was not protective. This epistatic interaction together with varying frequencies of α(+)thalassemia across Africa may explain the inconsistent relationship between Hp genotype and malaria reported in previous studies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.