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


METHODS
The 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.


RESULTS
By 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).


CONCLUSIONS
These 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.
['van Loon|Welmoed|W|http://orcid.org/0000-0003-3331-3997', 'Gai|Prabhanjan P|PP|', 'Hamann|Lutz|L|', 'Bedu-Addo|George|G|', 'Mockenhaupt|Frank P|FP|']
D056704:Adaptive Immunity D000328:Adult D005260:Female D020022:Genetic Predisposition to Disease D005869:Ghana D006579:Heterozygote D006801:Humans D007113:Immunity, Innate D016015:Logistic Models D016778:Malaria, Falciparum D035683:MicroRNAs D016017:Odds Ratio D010963:Plasmodium falciparum D016133:Polymerase Chain Reaction D020641:Polymorphism, Single Nucleotide D011247:Pregnancy D015597:Pregnancy Complications, Parasitic D011295:Prenatal Care D055815:Young Adult
MiRNA-146a Polymorphism Malaria Pregnancy Plasmodium falciparum Innate immunity