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MIR146A and ADIPOQ genetic variants are associated with birth weight in relation to gestational age: a cohort study

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the genetic variants related to polycystic ovary syndrome (PCOS) and its metabolic complications in girls born small for gestational age (SGA).

Design

Retrospective birth cohort study.

Materials and methods

We evaluated 66 women of reproductive age born at term (37–42 weeks of gestational age) according to the birth weight in relation to gestational age: 26 SGA and 40 AGA (Adequate for gestational age). Anthropometric and biochemical characteristics were measured, as well as the PCOS prevalence. We analyzed 48 single nucleotide polymorphisms (SNPs) previously associated with PCOS and its comorbidities using TaqMan Low-Density Array (TLDA). miRNet and STRING databases were used to predict target and disease networks.

Results

Anthropometric and biochemical characteristics did not differ between the SGA and AGA groups, as well as insulin resistance and PCOS prevalence. Two SNPs were not in Hardy–Weinberg equilibrium, the rs2910164 (MIR146A C > G) and rs182052 (ADIPOQ G > A). The rs2910164 minor allele frequency (MAF) was increased in SGA (OR, 2.77; 95%; CI, 1.22—6.29), while the rs182052 was increased AGA (OR, 0.34; 95%; CI, 0.13 – 0.88). The alleles related to reduced miRNA-146a (C) and ADIPOQ (A) activity showed increased frequency in SGA. The mature miR-146a targets 319 genes, been the CXCR4, TMEM167A and IF144L common targets and contributes to PCOS. The ADIPOQ main protein interactions were ERP44, PPARGCIA and CDH13.

Conclusions

The miR-146a (rs2910164) and ADIPOQ (rs182052) allelic variants are related to birth weight in SGA and may predict health-related outcomes, such as PCOS and obesity risk.

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Acknowledgements

The authors are extremely grateful to the subjects and their families for participating in this study. We also thank the members of the Human Reproduction Division at Department of Gynecology and Obstetrics of the Ribeirao Preto Medical School, University of Sao Paulo, especially Cristiana Carolina Padovan for the assistance in DNA quantification, Océlia de Vasconcelos for blood collection and Maria Albina Valladas Verceze and Tatiana Marina Vieira Giorgenon for measuring hormone concentrations.

Funding

This study was supported by the Sao Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP) with the grant 2015/26152–7 (RAF), National Council for Scientific and Technological Development (CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico), Coordination for the Improvement of Higher Education Personnel (CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Academic Excellence Program—PROEX and Graduate Support Program—PROAP) and the National Institutes of Science and Technology (INCT, Institutos Nacionais de Ciência e Tecnologia).

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Author notes

  1. Lívia Reis Silva, Anderson Sanches Melo, Cristiana Libardi Miranda Furtado and Rui Alberto Ferriani contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Ribeirao Preto Medical School (FMRP), University of Sao Paulo (USP), Ribeirão Preto, Brazil

    Lívia Reis Silva, Anderson Sanches Melo, Suleimy Cristina Mazin, Viviane Cunha Cardoso, Rosana Maria dos Reis, Cristiana Libardi Miranda Furtado & Rui Alberto Ferriani

  2. Fertility Center of Ribeirão Preto (CEFERP), Ribeirao Preto, Brasil

    Anderson Sanches Melo

  3. Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil

    Karina Bezerra Salomão & Luiz Gonzaga Tone

  4. Experimental Biology Center (NUBEX), University of Fortaleza (UNIFOR), Av. Washington Soares, 1321 - Edson Queiroz, Fortaleza, CEP 60811-905, Brazil

    Cristiana Libardi Miranda Furtado

  5. Drug Research and Development Center, Postgraduate Program in Translational Medicine (NPDM), Federal University of Ceará (UFC), Fortaleza, Brazil

    Cristiana Libardi Miranda Furtado

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  1. Lívia Reis Silva
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Silva, L.R., Melo, A.S., Salomão, K.B. et al. MIR146A and ADIPOQ genetic variants are associated with birth weight in relation to gestational age: a cohort study. J Assist Reprod Genet 39, 1873–1886 (2022). https://doi.org/10.1007/s10815-022-02532-x

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