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.
Programa de Pós-Graduação em Medicina, Neurologia/Neurociências, HUAP, Universidade Federal Fluminense (UFF), Niterói, Rio de Janeiro, Brazil.
Hum Cell. 2022 May;35(3):849-855. doi: 10.1007/s13577-022-00686-5. Epub 2022 Feb 26.
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 influence 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. Genotyping 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 significant difference 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.
非整倍体，如唐氏综合征（DS），是妊娠丢失的主要原因。极光激酶蛋白的异常导致基因组不稳定和非整倍体，主要发生在肿瘤中。因此，极光激酶基因的多态性可能会影响 DS 和自然流产的发生。进行了一项病例对照研究，纳入了 124 名 DS 患儿的母亲（DSM）和 219 名对照母亲（CM），以研究 AURKA 和 AURKC 多态性与 DS 风险的关系。采用 TaqMan 实时 PCR 进行基因分型。在 DSM 中，AURKA rs2273535 的次要等位基因频率（MAF）分别为 0.23，CM 中的频率为 0.20；而 AURKC rs758099 T 等位基因的频率在病例中为 0.32，在对照组中为 0.33。统计分析显示，DSM 和 CM 之间基因型和等位基因频率的分布无显著差异。根据自然流产的既往史，AURKA rs2273535 基因型（TT+AT 与 AA：OR 2.54，95%CI 1.13-5.71，p=0.02；AT 与 AA：OR 2.39，95%CI 1.03-5.51，p=0.04；T 与 A：OR 2.08，95%CI 1.12-3.90，p=0.02）和 AURKC rs758099（TT 与 CC：OR 4.34，95%CI 1.03-18.02，p=0.04；TT+CT 与 CC：OR 2.52，95%CI 1.02-6.23，p=0.04；T 与 C：OR 2.03，95%CI 1.09-3.80，p=0.02）在病例母亲中被观察为自然流产的危险因素。我们的研究表明，AURKA/AURKC 变异与唐氏综合征母亲自然流产风险增加之间可能存在关联。
