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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F22%3A10444150" target="_blank" >RIV/00216208:11150/22:10444150 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/22:10444150

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=fz2cCgBp4G" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=fz2cCgBp4G</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biology11030447" target="_blank" >10.3390/biology11030447</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Simple Summary Fetuses with hypotrophy (FGR, fetal growth restriction) are too small for their gestational age and may be prone to various diseases and loss of life. This study aimed to determine the role of single nucleotide polymorphisms (SNPs), located in two homeotic and two angiogenesis-related genes, in the occurrence of FGR, by analyzing blood samples from 380 women in singleton pregnancies. We found that the AT heterozygotes in HLX rs868058 were significantly associated with an approximately two-fold increased risk of FGR, diagnosed before 32 weeks of gestation (early-onset FGR). AT heterozygotes were significantly more frequent in women with early-onset FGR than in those with late-onset FGR (diagnosed from 32 weeks of gestation) and compared with healthy subjects. In conclusion, the AT genotype in HLX rs868058 may be a significant risk factor for the development of early-onset FGR. So far, the only therapeutic strategy for the management of early-onset FGR is to monitor and terminate pregnancy when the risk of fetal immaturity is lower than the risk of intrauterine death. Therefore, the disclosure of the mechanisms of action of the heterozygous AT state in HLX rs868058 would be important to identify plausible targets for new therapeutic approaches to treat the condition. 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 &gt; 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 &lt;= 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

Simple Summary Fetuses with hypotrophy (FGR, fetal growth restriction) are too small for their gestational age and may be prone to various diseases and loss of life. This study aimed to determine the role of single nucleotide polymorphisms (SNPs), located in two homeotic and two angiogenesis-related genes, in the occurrence of FGR, by analyzing blood samples from 380 women in singleton pregnancies. We found that the AT heterozygotes in HLX rs868058 were significantly associated with an approximately two-fold increased risk of FGR, diagnosed before 32 weeks of gestation (early-onset FGR). AT heterozygotes were significantly more frequent in women with early-onset FGR than in those with late-onset FGR (diagnosed from 32 weeks of gestation) and compared with healthy subjects. In conclusion, the AT genotype in HLX rs868058 may be a significant risk factor for the development of early-onset FGR. So far, the only therapeutic strategy for the management of early-onset FGR is to monitor and terminate pregnancy when the risk of fetal immaturity is lower than the risk of intrauterine death. Therefore, the disclosure of the mechanisms of action of the heterozygous AT state in HLX rs868058 would be important to identify plausible targets for new therapeutic approaches to treat the condition. 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 &gt; 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 &lt;= 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30214 - Obstetrics and gynaecology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biology

ISSN

2079-7737

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

17

Strana od-do

447

Kód UT WoS článku

000775765200001

EID výsledku v databázi Scopus

2-s2.0-85127576832