Beyond Genome-wide Scan: Association of a Cis-regulatory NCR3 Variant with Mild Malaria in a Population Living in the Republic of Congo

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Nov 10

PMID 29121672

Citations 4

Authors

Sabrina Baaklini

Sarwat Afridi

Thy Ngoc Nguyen

Felix Koukouikila-Koussounda

Mathieu Ndounga

Jean Imbert

Magali Torres

Lydie Pradel

Francine Ntoumi

Pascal Rihet

Affiliations

Soon will be listed here.

Abstract

Linkage studies have revealed a linkage of mild malaria to chromosome 6p21 that contains the NCR3 gene encoding a natural killer cell receptor, whereas NCR3-412G>C (rs2736191) located in its promoter region was found to be associated with malaria in Burkina Faso. Here we confirmed the association of rs2736191 with mild malaria in a Congolese cohort and investigated its potential cis-regulatory effect. Luciferase assay results indicated that rs2736191-G allele had a significantly increased promoter activity compared to rs2736191-C allele. Furthermore, EMSAs demonstrated an altered binding of two nuclear protein complexes to the rs2736191-C allele in comparison to rs2736191-G allele. Finally, after in silico identification of transcription factor candidates, pull-down western blot experiments confirmed that both STAT4 and RUNX3 bind the region encompassing rs2736191 with a higher affinity for the G allele. To our knowledge, this is the first report that explored the functional role of rs2736191. These results support the hypothesis that genetic variation within natural killer cell receptors alters malaria resistance in humans.

Citing Articles

Human NCR3 gene variants rs2736191 and rs11575837 alter longitudinal risk for development of pediatric malaria episodes and severe malarial anemia.

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Activatory Receptor NKp30 Predicts NK Cell Activation During Controlled Human Malaria Infection.

Walk J, Sauerwein R Front Immunol. 2020; 10:2864.

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First genome-wide association study of non-severe malaria in two birth cohorts in Benin.

Milet J, Boland A, Luisi P, Sabbagh A, Sadissou I, Sonon P Hum Genet. 2019; 138(11-12):1341-1357.

PMID: 31667592 DOI: 10.1007/s00439-019-02079-5.

polymorphism, haematological parameters, and severe malaria in Senegalese patients.

Thiam A, Baaklini S, Mbengue B, Nisar S, Diarra M, Marquet S PeerJ. 2018; 6:e6048.

PMID: 30533319 PMC: 6282937. DOI: 10.7717/peerj.6048.

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