MiRNA-146a polymorphism increases the odds of malaria in pregnancy

Welmoed Van Loon,George Bedu-Addo,Lutz Hamann,Prabhanjan P Gai,Frank P Mockenhaupt

doi:10.1186/s12936-019-2643-z

Abstract

BackgroundPlasmodium falciparum infection during pregnancy is a major cause of poor maternal health, adverse foetal outcome and infant mortality in sub-Saharan Africa. Genetic disposition is involved in susceptibility to malaria in pregnancy and its manifestation. MicroRNAs (miRNAs) influence gene regulation including that of innate immune responses. A miRNA-146a rs2910164 G > C single nucleotide polymorphism (SNP) has been associated with increased risks of several diseases, but no data as to malaria are available.MethodsThe association between miRNA-146a rs2910164 and P. falciparum infection among 509 Ghanaian women attending antenatal care (ANC) and 296 delivering Ghanaian primiparae was investigated. Malaria parasites were diagnosed by microscopy and PCR. Leukocyte-associated hemozoin in placental samples was recorded as well. Proportions were compared between groups by Fisher’s exact test, and logistic regression models were used to adjust for possible confounders.ResultsBy PCR, P. falciparum infection was detected in 63% and 67% of ANC attendees and delivering primiparae, respectively. In both groups, two in three women were either heterozygous or homozygous for miRNA-146a rs2910164. Among ANC attendees, homozygosity conferred increased odds of infection (adjusted odds ratio (aOR), 2.3; 95% CI, 1.3–4.0), which was pronounced among primigravidae (aOR, 5.8; 95% CI, 1.6–26) but only marginal in multigravidae. Likewise, homozygosity for miRNA-146a rs2910164 in primiparae increased the odds of past or present placental P. falciparum infection almost six-fold (aOR, 5.9; 95% CI, 2.1–18).ConclusionsThese results indicate that SNP rs2910164 G > C is associated with increased odds for P. falciparum infection in first-time pregnant women who are considered to lack sufficient acquired immune responses against pregnancy-specific strains of P. falciparum. These findings suggest that miRNA-146a is involved in protective malarial immunity, and specifically in the innate component.

Highlights

Plasmodium falciparum infection during pregnancy is a major cause of poor maternal health, adverse foetal outcome and infant mortality in sub-Saharan Africa
Plasmodium falciparum infection during pregnancy is a major cause of poor maternal health, miscarriage, stillbirth, low birth weight (LBW), preterm delivery and infant mortality in sub-Saharan Africa
The association of single nucleotide polymorphisms (SNPs) in genes encoding toll-like receptors (TLRs) and other members of the innate immune system with susceptibility to malaria in Sub-Saharan African populations [4, 5] suggests that SNPs in other immune regulators such as micro-RNAs influence malaria as well

Summary

Introduction

Plasmodium falciparum infection during pregnancy is a major cause of poor maternal health, adverse foetal outcome and infant mortality in sub-Saharan Africa. The association of single nucleotide polymorphisms (SNPs) in genes encoding toll-like receptors (TLRs) and other members of the innate immune system with susceptibility to (severe) malaria in Sub-Saharan African populations [4, 5] suggests that SNPs in other immune regulators such as micro-RNAs (miRNAs) influence malaria as well. MiRNAs are a class of small, non-coding, evolutionarily conserved RNA strains of approximately 22 nucleotides, and they are involved in gene regulation by their posttranslational action at the 3′-UTR region of mRNA. They control many processes, including pathways in the innate and adaptive immune responses [6]. SNP rs2910164 in the passenger strand of pre-miRNA-146a has been linked with both decreased and increased risk to various types of cancer [10], autoimmune diseases [11] and increased susceptibility of mycobacterial infections [12, 13]

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