Smith, Caren E.Coltell, OscarSorli, Jose V.Estruch, RamonAngel Martinez-Gonzalez, MiguelSalas-Salvado, JordiFito, MontserratAros, FernandoDashti, Hassan S.Lai, Chao Q.Miro, LeticiaSerra-Majem, LluisGomez-Gracia, EnriqueFiol, MiquelRos, EmilioAslibekyan, StellaHidalgo, BerthaNeuhouser, Marian L.Di, ChongzhiTucker, Katherine L.Arnett, Donna KOrdovas, Jose MCorella, Dolores2017-10-202017-10-202016Sci Rep. 2016; 6:331882045-2322http://hdl.handle.net/20.500.13003/10195http://hdl.handle.net/20.500.12105/5182Controversy 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.engVoRhttp://creativecommons.org/licenses/by/4.0/FOOD-FREQUENCY QUESTIONNAIRESINGLE-NUCLEOTIDE POLYMORPHISMLACTASE-PERSISTENCE PHENOTYPEDOSE-RESPONSE METAANALYSISMETABOLIC RISK-FACTORSDAIRY CONSUMPTIONUNITED-STATESPUERTO-RICANBODY-WEIGHTDIETCardiovascular DiseasesAgedGenetic MarkersMinichromosome Maintenance Complex Component 6United StatesAllelesHumansMendelian Randomization AnalysisMediterranean RegionMiddle AgedMaleMilkSex FactorsFemaleAnimalsDiet, MediterraneanAtribución 4.0 Internacional27624874610.1038/srep33188Scientific Reportsopen accessDieta MediterráneaAnimalesComponente 6 del Complejo de Mantenimiento de MinicromosomaAnálisis de la Aleatorización MendelianaLecheFemeninoMasculinoAlelosFactores SexualesHumanosRegión MediterráneaPersona de Mediana EdadAncianoEnfermedades CardiovascularesMarcadores GenéticosEstados Unidos2-s2.0-84987723109383196900001L622407296