Rs868058 in the Homeobox Gene HLX Contributes to Early-Onset Fetal Growth Restriction

• Published in: Biology (Basel, Switzerland) Vol. 11; no. 3; p. 447
• Main Authors: Wujcicka, Wioletta Izabela, Kacerovsky, Marian, Krekora, Michał, Kaczmarek, Piotr, Leśniczak, Beata, Grzesiak, Mariusz
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.03.2022; MDPI
• Subjects: Age; anemia; Angiogenesis; Asthma; Automation; blood; Blood platelets; Dental caries; fetal development; Fetuses; FGR; Genes; Gestational age; Gynecology; heterozygosity; Heterozygotes; HLX; Homeobox; homeobox genes; homeotic genes; Infections; Obstetrics; Placenta; Polymorphism; Pregnancy; Risk factors; Single-nucleotide polymorphism; SNP; Transcription factors; Ultrasonic imaging; Veins & arteries; Poland; Japan; FGR; SNP; HLX; angiogenesis; pregnancy; homeobox genes
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology11030447

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 DLX3 (rs11656951, rs2278163, and rs10459948), HLX (rs2184658, and 868058), ANGPT2 (−35 G > C), and ITGAV (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 HLX rs868058 were significantly associated with an approximately two-fold increase in disease risk (p ≤ 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, p = 0.022), and after being adjusted by anemia, in the codominant model (OR 2.45 95% CI 1.23–4.90, p = 0.034). In conclusion, the heterozygous AT genotype in HLX rs868058 can be considered a significant risk factor for the development of early-onset FGR, regardless of adverse pregnancy outcomes in women.