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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, Caren E
Coltell, Oscar
Sorlí, Jose V
Estruch, Ramón
Martínez-González, Miguel Ángel
Salas-Salvadó, Jordi
Fitó, Montserrat
Arós, Fernando
Dashti, Hassan S
Lai, Chao Q
Miró, Leticia
Serra-Majem, Lluís
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
metadata.dc.subject.mesh: Aged
Cardiovascular Diseases
Diet, Mediterranean
Genetic Markers
Mediterranean Region
Mendelian Randomization Analysis
Middle Aged
Minichromosome Maintenance Complex Component 6
Sex Factors
United States
Issue Date: 14-Sep-2016
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.
metadata.dc.identifier.doi: 10.1038/srep33188
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