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Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.

ABSTRACT: We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)-control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)_allelic = 0.63/p_perm = 0.0003; OR_additive = 0.61/p_perm = 0.001; OR_dominant = 0.56/p_perm = 0.001), NKX2-1 (rs999460) (effect allele A-OR_allelic = 1.37/p_perm = 0.003; OR_additive = 1.45/p_perm = 0.002; OR_recessive = 2.41/p_perm = 0.0002), GPRC5B (rs12444979) (effect allele T-OR_allelic = 1.67/p_perm = 0.0003; OR_dominant = 1.59/p_perm = 0.011; OR_additive = 1.56/p_perm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/p_perm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (p_perm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk.

SUBMITTER: Reshetnikov E

PROVIDER: S-EPMC10932237 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.

Reshetnikov Evgeny E Churnosova Maria M Reshetnikova Yuliya Y Stepanov Vadim V Bocharova Anna A Serebrova Victoria V Trifonova Ekaterina E Ponomarenko Irina I Sorokina Inna I Efremova Olga O Orlova Valentina V Batlutskaya Irina I Ponomarenko Marina M Churnosov Vladimir V Aristova Inna I Polonikov Alexey A Churnosov Mikhail M

International journal of molecular sciences 20240224 5

We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)-control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (log ...[more]

PMID: 38473894

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Project description:ObjectiveTo examine whether first trimester fetal growth restriction correlates with cardiovascular outcomes in childhood.DesignPopulation based prospective cohort study.SettingCity of Rotterdam, the Netherlands.Participants1184 children with first trimester fetal crown to rump length measurements, whose mothers had a reliable first day of their last menstrual period and a regular menstrual cycle.Main outcomes measuresBody mass index, total and abdominal fat distribution, blood pressure, and blood concentrations of cholesterol, triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7-6.8) years. Clustering of cardiovascular risk factors was defined as having three or more of: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations.ResultsOne standard deviation score greater first trimester fetal crown to rump length was associated with a lower total fat mass (-0.30%, 95% confidence interval -0.57% to -0.03%), android fat mass (-0.07%, -0.12% to -0.02%), android/gynoid fat mass ratio (-0.53, -0.89 to -0.17), diastolic blood pressure (-0.43, -0.84 to -0.01, mm Hg), total cholesterol (-0.05, -0.10 to 0, mmol/L), low density lipoprotein cholesterol (-0.04, -0.09 to 0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk 0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and weight at birth changed these effect estimates only slightly. Childhood body mass index fully explained the associations of first trimester fetal crown to rump length with childhood total fat mass. First trimester fetal growth was not associated with other cardiovascular outcomes. Longitudinal growth analyses showed that compared with school age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown to rump length and lower second and third trimester estimated fetal weight but higher weight growth from the age of 6 months onwards.ConclusionsImpaired first trimester fetal growth is associated with an adverse cardiovascular risk profile in school age children. Early fetal life might be a critical period for cardiovascular health in later life.

Dataset Information

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.

Publications

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.

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