Association of maternal weight with FADS and ELOVL genetic variants and fatty acid levels- The PREOBE follow-up.

Andrea De La Garza Puentes,Preobe Team ,María Bonilla Aguirre,M Carmen Lopez-Sabater,Cristina Campoy,Maite Segura Moreno,Francisco José Torres-Espínola,Marcela Guerendiain,Rosa Montes Goyanes,Ana Isabel Castellote Bargalló,Luz García-Valdés,Leonor De Almeida,Miriam Arias García,Aida Maribel Chisaguano Tonato

doi:10.1371/journal.pone.0179135

Abstract

Single nucleotide polymorphisms (SNPs) in the genes encoding the fatty acid desaturase (FADS) and elongase (ELOVL) enzymes affect long-chain polyunsaturated fatty acid (LC-PUFA) production. We aimed to determine if these SNPs are associated with body mass index (BMI) or affect fatty acids (FAs) in pregnant women. Participants (n = 180) from the PREOBE cohort were grouped according to pre-pregnancy BMI: normal-weight (BMI = 18.5–24.9, n = 88) and overweight/obese (BMI≥25, n = 92). Plasma samples were analyzed at 24 weeks of gestation to measure FA levels in the phospholipid fraction. Selected SNPs were genotyped (7 in FADS1, 5 in FADS2, 3 in ELOVL2 and 2 in ELOVL5). Minor allele carriers of rs174545, rs174546, rs174548 and rs174553 (FADS1), and rs1535 and rs174583 (FADS2) were nominally associated with an increased risk of having a BMI≥25. Only for the normal-weight group, minor allele carriers of rs174537, rs174545, rs174546, and rs174553 (FADS1) were negatively associated with AA:DGLA index. Normal-weight women who were minor allele carriers of FADS SNPs had lower levels of AA, AA:DGLA and AA:LA indexes, and higher levels of DGLA, compared to major homozygotes. Among minor allele carriers of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher DHA:EPA index than the normal-weight group; however, they did not present higher DHA concentrations than the normal-weight women. In conclusion, minor allele carriers of FADS SNPs have an increased risk of obesity. Maternal weight changes the effect of genotype on FA levels. Only in the normal-weight group, minor allele carriers of FADS SNPs displayed reduced enzymatic activity and FA levels. This suggests that women with a BMI≥25 are less affected by FADS genetic variants in this regard. In the presence of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher n-3 LC-PUFA production indexes than women with normal weight, but this was not enough to obtain a higher n-3 LC-PUFA concentration.

Highlights

During pregnancy, the mother is the sole source of key nutrients for the fetus, such as n-6 and n-3 long-chain (LC) polyunsaturated fatty acids (PUFAs) [1,2,3]
In line with other studies [5, 12], we found that the FADS1 and FADS2 Single nucleotide polymorphisms (SNPs) were associated with FAs, mainly from the n-6 series, and less with those from the n-3 series
Enzymatic activity and FA levels were reduced in normal-weight women who were minor allele carriers of fatty acid desaturase (FADS) SNPs; these reductions were not significant in overweight/obese participants

Summary

Introduction

The mother is the sole source of key nutrients for the fetus, such as n-6 and n-3 long-chain (LC) polyunsaturated fatty acids (PUFAs) [1,2,3]. Hyperlipidemia develops in normal pregnancy; it has been observed that levels of fatty acid (FA), such as DHA, increase in maternal plasma during pregnancy. Due to the beneficial effects of n-3 LC-PUFAs, it is recommended to increase their intake during pregnancy [4]. This is in contrast with the effect of excessive n-6 FA intake, which may lead to maternal obesity and obesity-related complications such as an increased risk of cardiovascular disease [7, 8]. Obese pregnancies lead to a higher risk of obesity in newborn babies, thereby increasing the likelihood of lifelong obesity and obesity-related complications [9, 10]

Objectives

Methods

Results

Discussion

Conclusion