Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization

作者：Smith Caren E; Coltell Oscar; Sorli Jose V; Estruch Ramon; Angel Martinez Gonzalez Miguel; Salas Salvado Jordi; Fito Montserrat; Aros Fernando; Dashti Hassan S; Lai Chao Q; Miro Leticia; Serra Majem Lluis; Gomez Gracia Enrique; Fiol Miquel; Ros Emilio; Aslibekyan Stella; Hidalgo Bertha; Neuhouser Marian L; Di C*******; Tucker Katherine L; Arnett Donna K; Ordovas Jose M; Corella Dolores

来源：Scientific Reports, 2016, 6(1): 33188.

DOI：10.1038/srep33188

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.

• 出版日期2016-9-14
• 单位河北医科大学