Smith, Caren E.Fitó Colomer, MontserratCorella, Dolores2016-12-052016-12-052016Smith CE, Coltell O, Sorlí JV, Estruch R, Martínez-González MÁ, Salas-Salvadó J. et al. Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization. Sci Rep. 2016 Sep 14;6:33188. doi: 10.1038/srep331882045-2322http://hdl.handle.net/10230/27695Controversy persists on the association between dairy products, especially milk, and cardiovascular diseases (CVD). Genetic proxies may improve dairy intake estimations, and clarify diet-disease relationships through Mendelian randomization. We meta-analytically (n ≤ 20,089) evaluated associations between a lactase persistence (LP) SNP, the minichromosome maintenance complex component 6 (MCM6)-rs3754686C>T (nonpersistence>persistence), dairy intake, and CVD biomarkers in American (Hispanics, African-American and Whites) and Mediterranean populations. Moreover, we analyzed longitudinal associations with milk, CVD and mortality in PREDIMED), a randomized Mediterranean diet (MedDiet) intervention trial (n = 7185). The MCM6-rs3754686/MCM6-rs309180 (as proxy), LP-allele (T) was strongly associated with higher milk intake, but inconsistently associated with glucose and lipids, and not associated with CVD or total mortality in the whole population. Heterogeneity analyses suggested some sex-specific associations. The T-allele was associated with higher CVD and mortality risk in women but not in men (P-sex interaction:0.005 and 0.032, respectively), mainly in the MedDiet group. However, milk intake was not associated with CVD biomarkers, CVD or mortality either generally or in sub-groups. Although MCM6-rs3754686 is a good milk intake proxy in these populations, attributing its associations with CVD and mortality in Mediterranean women to milk is unwarranted, as other factors limiting the assumption of causality in Mendelian randomization may exist.application/pdfeng© 2016, The Author(s) This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Sistema cardiovascular -- Malalties -- Aspectes genèticsLlet -- Aspectes nutricionalsinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/srep33188info:eu-repo/semantics/openAccess