Aspectos genéticos e epigenéticos da amamentação

Abstract

Breastfeeding has clear short and long-term benefits to health and human capital. Possible biological mechanisms underlying these effects are epigenetic modifications – including DNA methylation – and the presence of long-chain polyunsaturated fatty acids (LC-PUFAs) in breast milk. In this, the relationship between breastfeeding and DNA methylation in the offspring was investigated through a systematic literature review (paper 1) and an original study using data on DNA methylation levels in hundreds of thousands of regions in the genome (paper 2). The role of LC-PUFAs in the association between breastfeeding and intelligence quotient (IQ) was also evaluated through the interaction between polymorphisms in the FADS2 gene (which encodes a key enzyme for the endogenous synthesis of LC-PUFAs) and breastfeeding, with IQ being the outcome (paper 3). This analysis tested a nutritional adequacy hypothesis, which postulates that the benefits of breastfeeding on IQ are larger among carriers of genotypes associated with lower endogenous synthesis of LC-PUFAs (and therefore more dependent on pre-formed LC-PUFAs). In paper 1, it was verified that the literature on the relationship between breastfeeding and DNA methylation is scarce, and the few available studies have important limitations. In paper 2, which used data from a British birth cohort, breastfeeding was found to be associated with blood DNA methylation levels at the age of 7 years, and some of these associations persisted until adolescence. In paper 3, which was based on a de novo meta-analysis including both published and unpublished data, IQ was on average higher among individuals that were breastfed in both genetic groups, with no indication of the FADS2-breastfeeding interaction, thus arguing against the nutritional adequacy hypothesis. However, complementary analyses suggested that this hypothesis might be true, but detecting the interaction would require that the average duration of breastfeeding in the included studies were higher. Collectively, the results from these three papers indicate that breastfeeding is associated with persistent epigenetic modifcations, and that breastfeeding is positively associated with IQ benefits in all genotypes with respect to the studied polymorphisms.