KIR and HLA-C: Immunogenetic regulation of human birth weight

  • Lydia E. Farrell
  • Susan E. Hiby
  • Richard Apps
  • Olympe Chazara
  • Lill Trogstad
  • Håkon K. Gjessing
  • Per Magnus
  • Mary Carrington
  • Ashley Moffett

Abstract

Pregnancies resulting in very small or very large babies are at higher risk of obstetric complications with increased morbidity for both mother and baby. Using data from the Medical Birth Registry of Norway we have shown how human birth weight is still subject to stabilizing selection. Particular combinations of maternal/fetal immune genes have been implicated in pregnancies resulting in a low birth weight baby (<5th birth weight centile). More specifically, an inhibitory maternal KIRAA genotype with a paternally derived fetal HLA-C2 ligand. At the other end of the birth weight spectrum the presence of an activating maternal KIR2DS1 gene is associated with increased birth weight in linear or logistic regression analyses of all pregnancies >5th centile (p=0.005, OR=2.65). Thus, inhibitory maternal KIR combined with fetal HLA-C2 is more frequently associated with low birth weight, whereas activating maternal KIR with fetal HLA-C2 ligand is associated with increasing birth weight. Our findings using the MoBa cohort have replicated the association of KIR and HLA-C seen in poor placentation, and confirm the importance of maternal/fetal immune gene interactions in determining the outcome of pregnancy.

Author Biographies

Lydia E. Farrell
Susan E. Hiby
Richard Apps
Olympe Chazara
Lill Trogstad
Håkon K. Gjessing
Per Magnus
Mary Carrington
Ashley Moffett
Published
2014-12-29
How to Cite
Farrell, L. E., Hiby, S. E., Apps, R., Chazara, O., Trogstad, L., Gjessing, H. K., Magnus, P., Carrington, M., & Moffett, A. (2014). KIR and HLA-C: Immunogenetic regulation of human birth weight. Norsk Epidemiologi, 24(1-2). https://doi.org/10.5324/nje.v24i1-2.1810