Vol.:(0123456789) 1 3
Human Cell (2022) 35:849–855
https://doi.org/10.1007/s13577-022-00686-5
RESEARCH ARTICLE
Aurora kinase genetic polymorphisms: an association study in Down
syndrome and spontaneous abortion
Carolina Monteiro Leite de Castro
1,4
· Carolina Oliveto Bastos Pereira
1
· Joissy Aprigio
1
· Marcelo A. Costa Lima
2
·
Márcia G. Ribeiro
3
· Márcia Rodrigues Amorim
1,4
Received: 15 November 2021 / Accepted: 10 February 2022 / Published online: 26 February 2022
© The Author(s) under exclusive licence to Japan Human Cell Society 2022
Abstract
Aneuploidies, such as Down syndrome (DS), are the leading cause of pregnancy loss. Abnormalities in aurora kinase proteins
result in genomic instability and aneuploidy, mainly in tumors. Thus, polymorphisms in Aurora kinase genes could infuence
the occurrence of DS and spontaneous abortion. A case-control study was conducted including 124 mothers of DS children
(DSM) and 219 control mothers (CM) to investigate DS risk according to AURKA and AURKC polymorphisms. Genotyp-
ing was performed using TaqMan real-time PCR. The minor allele frequency (MAF) observed in AURKA rs2273535 was,
respectively, 0.23 in DSM and 0.20 in CM, whereas the frequency of the AURKC rs758099 T allele was 0.32 in case and 0.33
in control mothers. Statistical analysis showed no signifcant diference in the distribution of genotypes and allele frequencies
between DSM and CM. According to previous history of spontaneous abortion, the AURKA rs2273535 genotypes (TT + AT
vs. AA: OR 2.54, 95% CI 1.13–5.71, p = 0.02; AT vs. AA: OR 2.39, 95% CI 1.03–5.51, p = 0.04; T vs. A: OR 2.08, 95% CI
1.12–3.90, p = 0.02) and AURKC rs758099 (TT vs. CC: OR 4.34, 95% CI 1.03–18.02, p = 0.04; TT + CT vs. CC: OR 2.52,
95% CI 1.02–6.23, p = 0.04; T vs. C: OR 2.03, 95% CI 1.09–3.80, p = 0.02) were observed as risk factors for spontaneous
abortion in case mothers. Our study suggests a possible relationship between AURKA/AURKC variants and increased risk
of spontaneous abortion within Down syndrome mothers.
Keywords Down syndrome · AURKA · AURKC · Aneuploidy · Polymorphisms
Introduction
Aneuploidy is the most frequent chromosome abnormality
in humans, occurring in at least 10% of all pregnancies [1].
This genetic imbalance originated from non-disjunction of
chromosomes, results frequently in monosomies and tri-
somies. Aneuploidy is the leading cause of miscarriages,
chromosomes 16, 21 and 22 account for almost 50% of all
trisomies identifed in spontaneous abortion. In conceptions
that survive to term, aneuploidy is the commonest cause of
intellectual and developmental disabilities [1, 2].
Down syndrome (DS) is the most prevalent viable ane-
uploidy worldwide. Its occurrence is most commonly a
result of an extra chromosome 21 which emerges from a
meiotic missegregation, especially during maternal meio-
sis I (MI) division. This syndrome may also occur due to
Robertsonian translocation or mosaicism [2, 3]. Advanced
maternal age at conception is a well-known risk factor
for pregnancy loss and trisomies, including DS [ 4, 5].
However, the molecular mechanisms of chromosomal
* Márcia Rodrigues Amorim
marciaamorim@id.uf.br
1
Laboratório de Genética Humana, Departamento de
Biologia Geral, Instituto de Biologia, Universidade Federal
Fluminense, Rua Prof. Marcos Waldemar de Freitas Reis-
São Domingos, Niterói, RJ 24210-201, Brazil
2
Departamento de Genética, Instituto de Biologia Roberto
Alcântara Gomes, Universidade do Estado do Rio de
Janeiro, Rua São Francisco Xavier 524, PHLC, Maracanã,
Rio de Janeiro, RJ 20550-900, Brazil
3
Instituto de Puericultura e Pediatria Martagão Gesteira,
Universidade Federal do Rio de Janeiro, Rua Bruno Lobo
50, Cidade Universitária-Ilha Do Fundão, Rio de Janeiro,
RJ 21941-912, Brazil
4
Programa de Pós-Graduação em Medicina,
Neurologia/Neurociências, HUAP, Universidade Federal
Fluminense (UFF), Niterói, Rio de Janeiro, Brazil