Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/42439
Title: Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization
Authors: Smith, C.E.
Coltell, O.
Sorlí, J.V.
Estruch, R. 
Martínez-González, M.Á.
Salas-Salvadó, J.
Fitó, M.
Arós, F.
Dashti, H.S.
Lai, C.Q.
Miró, L.
Serra Majem, Liuís 
Gómez-Gracia, Enrique
Fiol, Miquel
Ros, Emilio 
Aslibekyan, Stella
Hidalgo, Bertha
Neuhouser, Marian L.
Di, Chongzhi
Tucker, Katherine L.
Arnett, Donna K.
Ordovás, José M.
Corella, Dolores
UNESCO Clasification: 3206 Ciencias de la nutrición
Keywords: Food-Frequency Questionnaire
Single-Nucleotide Polymorphism
Lactase-Persistence Phenotype
Dose-Response Metaanalysis
Metabolic Risk-Factors
Dairy Consumption
United-States
Puerto-Rican
Body-Weight
Diet
Issue Date: 2016
Journal: Scientific Reports 
Abstract: Controversy 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.
URI: http://hdl.handle.net/10553/42439
ISSN: 2045-2322
DOI: 10.1038/srep33188
Source: Scientific Reports [ISSN 2045-2322], v. 6, article number 33188
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