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

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 b...

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Authors: E. Smith, C. (Caren)|||/items/7c4824c0-890c-4f0a-9c41-1e0217cbd4a9, Coltell, O. (Oscar)|||/items/0570478b-e457-4f41-849f-4494755b27a8, Sorli, J.V. (Jose V.)|||/items/4df644ee-a292-4fe6-a493-f23c7ff830f6, Estruch, R. (Ramón)|||/items/3e95ff5c-8b32-474d-a8d4-7b1425d89265, Martínez-González, M.A. (Miguel Ángel)|||/items/8b591471-4165-4697-8534-cfa0ad5eb1b7, Salas-Salvado, J. (Jordi)|||/items/e2fc08dd-d21f-475b-83fa-157f0b0067e6, Fito, M. (Montserrat)|||/items/7de631e9-926b-4b1a-9964-0c0ca699df6b, Aros, F. (Fernando)|||/items/399e060f-9616-4d06-a6fd-9a2b2badc2ce, S. Dashti, H. (Hassan)|||/items/73a14524-2edb-495f-bf1b-a595d4afe641, Q. Lai, C. (Chao)|||/items/266384e1-771a-4a91-aa82-54a95f0537c3, Miro, L. (Leticia)|||/items/37a29f1f-9207-4e08-82a0-82204acbf4f8, Serra-Majem, L. (Luis)|||/items/2b0e8280-1783-4e01-8f35-cc7161c52ff7, Gomez-Gracia, E. (Enrique)|||/items/89359409-0217-44dd-94b0-14f45dba2c99, Fiol, M. (Miquel)|||/items/5d318070-a49f-4a89-8633-7809d4934fa2, Ros, E. (Emilio)|||/items/8c9fcd5a-f4ca-4a48-8fad-4737d7d5ca7f, Aslibekyan, S. (Stella)|||/items/5fbe6c2b-e2f9-44e3-af24-08b44ab513fd, Hidalgo, B. (Berta)|||/items/e7964944-c1e8-40aa-aae9-f8f706223f30, L. Neuhouser, M. (Marian)|||/items/4080ddb6-810a-4098-ae68-1dd46d2f4e9e, Di, C. (Chongzhi)|||/items/5b8b08b3-6e59-4d23-b1d0-c0ebf1b0a009, L. Tucker, K. (Katherine)|||/items/a16f5012-c11b-4da2-b8c7-f0e7f5f724af, K. Arnett, D. (Donna)|||/items/918e92c3-f6c0-46f2-b0a1-f3e5b4c3b126, Ordovas, J.M. (Jose Maria)|||/items/47377f9c-3ded-4da9-9b70-5425df93cfcc, Corella, D. (Dolores)|||/items/edf5ac4d-018f-446d-aa6e-2448c41a1e41
Format: article
Publication Date:2016
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/41754
Online Access:https://hdl.handle.net/10171/41754
Access Level:Open access
Keyword:Mediterranean population
American population
Cardiovascular biomarkers
Disease
Mortality
Milk intake
Cardiovascular diseases (CVD)
Materias Investigacion::Ciencias de la Salud::Endocrinología
Materias Investigacion::Ciencias de la Salud::Medicina preventiva
Description
Summary: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.

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