Associations between single nucleotide polymorphisms and erythrocyte parameters in humans: A systematic literature review

Tiffany Timmer, Michael W.T. Tanck, Elisabeth Huis in 't Veld, Barbera Veldhuisen, Joost G. Daams, Wim L.A.M. De Kort, C. Ellen Van Der Schoot, Katja Van Den Hurk

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)


Individual variations in erythrocyte parameters are influenced by factors like sex, age, diet and season. Genetic variations have also been associated with erythrocyte parameters. The aim of this systematic review is to provide an overview of associations between single nucleotide polymorphisms (SNPs) and erythrocyte parameters in humans. A systematic review protocol was published at the international prospective register of systematic reviews (registration number CRD42016053052). Literature searches were conducted in Medline and Embase. Studies were included if: investigating a(n) causality/association/correlation; population-based; investigating a human population of Caucasian/mixed-ethnic descent; and written in English, Dutch or German. Study quality was assessed using the quality of genetic association studies tool. In total, 4385 studies were screened on title/abstract and 194 studies were screened on full text. Inclusion criteria were met by 13 candidate gene studies (n = 126-49,488) and eight genome-wide association studies (GWASes, n = 1664-116,666). One moderate and six good quality GWAS(es) identified 1237 SNPs located in/near 241 genes. SNPs in/near ten genes were found to be associated with one or more erythrocyte parameter(s) by multiple GWASes, namely HIST1H2AC, MPST, SLC17A1 and SLC17A3 with mean cell hemoglobin (MCH), HIST1H1T and KCTD17 with MCH and mean cell volume (MCV), HBS1L and MYB with MCH, MCV and red cell count (RCC), HFE with MCH, MCV and hemoglobin, and TMPRSS6 with MCH, MCV, hemoglobin and mean cell hemoglobin concentration (MCHC). Four genes were found across multiple erythrocyte parameters by one study in each parameter. Fourteen SNPs were associated with one or more erythrocyte parameter(s) in multiple cohorts, namely rs129128, rs17342717, rs228129 and rs5756504 (MCH), rs4895441, rs7775698, rs9376092 and rs9494145 (MCH, MCV, RCC), rs6569992 (MCH, RCC), rs1800562 (hemoglobin, MCH, MCV), rs130624 and rs198846 (MCH, MCV), rs4820268 and rs855791 (MCH, MCV, MCHC). Further research on these fourteen genes in erythropoiesis is recommended, especially eight whose role in erythropoiesis is unclear.

Original languageEnglish
Pages (from-to)58-67
Number of pages10
JournalMutation Research/Reviews in Mutation Research
Publication statusPublished - 1 Jan 2019


  • AGE
  • GENE
  • Genome-wide association study
  • Hematocrit
  • Hemoglobin
  • Red cell count
  • Red cell indices
  • Systematic review


Dive into the research topics of 'Associations between single nucleotide polymorphisms and erythrocyte parameters in humans: A systematic literature review'. Together they form a unique fingerprint.

Cite this