Maternal Age at Menarche Gene Polymorphisms Are Associated with Offspring Birth Weight

Yuliya Reshetnikova; Maria Churnosova; Vadim Stepanov; Anna Bocharova; Victoria Serebrova; Ekaterina Trifonova; Irina Ponomarenko; Inna Sorokina; Olga Efremova; Valentina Orlova; Irina Batlutskaya; Marina Ponomarenko; Vladimir Churnosov; Natalya Eliseeva; Inna Aristova; Alexey Polonikov; Evgeny Reshetnikov; Mikhail Churnosov

doi:10.3390/life13071525

Maternal Age at Menarche Gene Polymorphisms Are Associated with Offspring Birth Weight

Life (Basel). 2023 Jul 7;13(7):1525. doi: 10.3390/life13071525.

Authors

Yuliya Reshetnikova¹, Maria Churnosova¹, Vadim Stepanov², Anna Bocharova², Victoria Serebrova², Ekaterina Trifonova², Irina Ponomarenko¹, Inna Sorokina¹, Olga Efremova¹, Valentina Orlova¹, Irina Batlutskaya¹, Marina Ponomarenko¹, Vladimir Churnosov¹, Natalya Eliseeva¹, Inna Aristova¹, Alexey Polonikov^{1

3}, Evgeny Reshetnikov¹, Mikhail Churnosov¹

Affiliations

¹ Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia.
² Research Institute for Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia.
³ Department of Biology, Medical Genetics and Ecology and Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia.

Abstract

In this study, the association between maternal age at menarche (AAM)-related polymorphisms and offspring birth weight (BW) was studied. The work was performed on a sample of 716 pregnant women and their newborns. All pregnant women underwent genotyping of 50 SNPs of AAM candidate genes. Regression methods (linear and Model-Based Multifactor Dimensionality Reduction (MB-MDR)) with permutation procedures (the indicator p_perm was calculated) were used to identify the correlation between SNPs and newborn weight (transformed BW values were analyzed) and in silico bioinformatic examination was applied to assess the intended functionality of BW-associated loci. Four AAM-related genetic variants were BW-associated including genes such as POMC (rs7589318) (β_additive = 0.202/p_perm = 0.015), KDM3B (rs757647) (β_recessive = 0.323/p_perm = 0.005), INHBA (rs1079866) (β_additive = 0.110/p_perm = 0.014) and NKX2-1 (rs999460) (β_recessive = -0.176/p_perm = 0.015). Ten BW-significant models of interSNPs interactions (p_perm ≤ 0.001) were identified for 20 polymorphisms. SNPs rs7538038 KISS1, rs713586 RBJ, rs12324955 FTO and rs713586 RBJ-rs12324955 FTO two-locus interaction were included in the largest number of BW-associated models (30% models each). BW-associated AAM-linked 22 SNPs and 350 proxy loci were functionally related to 49 genes relevant to pathways such as the hormone biosynthesis/process and female/male gonad development. In conclusion, maternal AMM-related genes polymorphism is associated with the offspring BW.

Keywords: age of menarche; association; birth weight; single nucleotide polymorphism.

Grants and funding

This research received no external funding.