Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk

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.