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Pediatrics

Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity

International Journal of Obesity volume 45, pages 56–65 (2021)Cite this article

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Abstract

Background

Several studies identified genetic variants in FADS and ELOVL2 genes associated with obesity-related conditions, such as alterations in blood lipid parameters and insulin homeostasis. The aim of this cross-sectional study was to determine whether FADS and ELOVL2 genetic variants were associated with obesity and adiposity, besides dyslipidaemia and insulin resistance, in a large sample of obese children and adolescents.

Materials and methods

One thousand six hundred and forty-nine obese children underwent physical examination, anthropometry, fasting blood tests measuring plasma glucose, lipid and liver profile. Two genetic variants were genotyped: rs2236212 in ELOVL2 gene and rs1535 in FADS2, for the gene cluster FADS. In a subgroup of obese children (n = 105), erythrocyte fatty acid composition was measured. Generalized linear models were used to assess association between genotypes and variables.

Results

A positive association between zBMI and the minor allele of rs2236212 (p = 0.028), the major allele of rs1535 (p = 0.046) and the genetic score (p = 0.008), created by summing up both risk alleles, were found. The estimation of enzymatic activity revealed that minor alleles were associated significantly with a reduction of the enzymatic activity of elongase and desaturase (p = 0.048 and p = 0.0001, respectively).

Discussion and conclusions

Common variants in the FADS2 and ELOVL2 genes were associated with BMI in a large population of obese Italian children. These SNPs were associated with alterations in LC-PUFAs homeostasis, not accompanied by modifications of plasma lipids or HOMA-IR. These findings provide additional support to the genetics accounting for BMI interindividual variability and the molecular basis of obesity.

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Fig. 1: FADS2 and ELOVL2 genetic score is associated with increased zBMI. Data are shown as mean (SEM).
Fig. 2: Association between genotypes of rs1535 (A) and rs2236212 (C) and the enzymatic activity and the products of D5D and elongase 2.

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Acknowledgements

We kindly thank the patients and their families who participated in the study.

Funding

Supported by grants FUR MAFFEIS from the University of Verona to CM. Part of the study was supported by a grant of the Italian Ministry of Health (GR-2011-02349630) to CF in agreement with the “Regione Veneto” and the “Azienda Ospedaliera Universitaria Integrata di Verona.”

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Authors and Affiliations

  1. Pediatric Diabetes and Metabolic Disorders, Department of Surgical Sciences, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy

    Alice Maguolo, Chiara Zusi, Anita Morandi & Claudio Maffeis

  2. Department of Medicine, General Medicine and Hypertension Unit, University of Verona, Verona, Italy

    Alice Giontella, Angela Tagetti & Cristiano Fava

  3. Department of the Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy

    Emanuele Miraglia Del Giudice

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  1. Alice Maguolo
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Contributions

A Maguolo, CZ, and AG researched and analyzed data and wrote the manuscript. A Maguolo, CZ, AG, AT, and A Morandi researched data and discussed the manuscript. EMDG, CF, A Morandi, and CM edited the manuscript, and provided substantial contribution to the overall discussion. CF and CM are the guarantor of this work and, as such, had full access to all the data in the study and take responsibility for the integrity and the accuracy of the data analysis.

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Correspondence to Claudio Maffeis.

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Supplementary information

41366_2020_662_MOESM1_ESM.docx

Supplementary table 1. Differences between the two groups of children undergoing fatty acids measurement in different biological matrices.

41366_2020_662_MOESM2_ESM.docx

Supplementary table 2: Differences of desaturases and elongase activities and fatty acids dosages according to the genotypes of FADS2 and ELOVL2 SNPs in the two groups of children undergoing fatty acids measurement, separately.

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Maguolo, A., Zusi, C., Giontella, A. et al. Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity. Int J Obes 45, 56–65 (2021). https://doi.org/10.1038/s41366-020-00662-9

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