Rs868058 in the Homeobox Gene <i>HLX</i> Contributes to Early-Onset Fetal Growth Restriction
2022
Wioletta Izabela Wujcicka | Marian Kacerovsky | Michał Krekora | Piotr Kaczmarek | Beata Leśniczak | Mariusz Grzesiak
Fetal growth restriction (FGR) is a condition that characterizes fetuses as too small for their gestational age, with an estimated fetal weight (EFW) below the 10th percentile and abnormal Doppler parameters and/or with EFW below the 3rd percentile. We designed our study to demonstrate the contribution of single nucleotide polymorphisms (SNPs) from <i>DLX3</i> (rs11656951, rs2278163, and rs10459948), <i>HLX</i> (rs2184658, and 868058), <i>ANGPT2</i> (−35 G > C), and <i>ITGAV</i> (rs3911238, and rs3768777) genes in maternal blood in FGR. A cohort of 380 women with singleton pregnancies consisted of 190 pregnancies with FGR and 190 healthy full-term controls. A comparison of the pregnancies with an early-onset FGR and healthy subjects showed that the AT heterozygotes in <i>HLX</i> rs868058 were significantly associated with an approximately two-fold increase in disease risk (<i>p</i> ≤ 0.050). The AT heterozygotes in rs868058 were significantly more frequent in the cases with early-onset FGR than in late-onset FGR in the overdominant model (OR 2.08 95% CI 1.11–3.89, <i>p</i> = 0.022), and after being adjusted by anemia, in the codominant model (OR 2.45 95% CI 1.23–4.90, <i>p</i> = 0.034). In conclusion, the heterozygous AT genotype in <i>HLX</i> rs868058 can be considered a significant risk factor for the development of early-onset FGR, regardless of adverse pregnancy outcomes in women.
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