PMID- 27624874
OWN - NLM
STAT- MEDLINE
DCOM- 20180531
LR  - 20240325
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Sep 14
TI  - Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and 
      American populations with cardiovascular biomarkers, disease and mortality: 
      Mendelian randomization.
PG  - 33188
LID - 10.1038/srep33188 [doi]
LID - 33188
AB  - 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.
FAU - Smith, Caren E
AU  - Smith CE
AD  - Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research 
      Center on Aging, Tufts University, Boston, MA, USA.
FAU - Coltell, Oscar
AU  - Coltell O
AD  - Department of Computer Languages and Systems, School of Technology and 
      Experimental Sciences. University Jaume I, Castellon, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
FAU - Sorli, Jose V
AU  - Sorli JV
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Department of Preventive Medicine and Public Health, School of Medicine, 
      University of Valencia, Valencia, Spain.
FAU - Estruch, Ramon
AU  - Estruch R
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, Spain.
FAU - Martinez-Gonzalez, Miguel Angel
AU  - Martinez-Gonzalez MA
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Department of Preventive Medicine and Public Health, University of 
      Navarra-Navarra Institute for Health Research (IdisNa), Pamplona, Navarra, Spain.
FAU - Salas-Salvado, Jordi
AU  - Salas-Salvado J
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Human Nutrition Unit, Biochemistry and Biotechnology Department, IISPV, 
      University Rovira i Virgili, Reus, Spain.
FAU - Fito, Montserrat
AU  - Fito M
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Cardiovascular Epidemiology Unit, Municipal Institut for Medical Research (IMIM), 
      Barcelona, Spain.
FAU - Aros, Fernando
AU  - Aros F
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Department of Cardiology, Hospital Txagorritxu, Vitoria, Spain.
FAU - Dashti, Hassan S
AU  - Dashti HS
AD  - Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research 
      Center on Aging, Tufts University, Boston, MA, USA.
FAU - Lai, Chao Q
AU  - Lai CQ
AD  - Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research 
      Center on Aging, Tufts University, Boston, MA, USA.
FAU - Miro, Leticia
AU  - Miro L
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Department of Family Medicine, Research Unit. Distrito Sanitario Atencion 
      Primaria Sevilla, Spain.
FAU - Serra-Majem, Lluis
AU  - Serra-Majem L
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Research Institute of Biomedical and Health Sciences, University of Las Palmas de 
      Gran Canaria, Las Palmas de Gran Canaria, Spain.
FAU - Gomez-Gracia, Enrique
AU  - Gomez-Gracia E
AD  - Department of Epidemiology, School of Medicine, University of Malaga, Malaga, 
      Spain.
FAU - Fiol, Miquel
AU  - Fiol M
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Palma Institute of Health Research (IdISPa). Hospital Son Espases. Palma de 
      Mallorca, Spain.
FAU - Ros, Emilio
AU  - Ros E
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Lipid Clinic, Endocrinology and Nutrition Service, Institut d'Investigacions 
      Biomediques August Pi Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain.
FAU - Aslibekyan, Stella
AU  - Aslibekyan S
AD  - Department of Epidemiology, School of Public Health, University of Alabama, 
      Birmingham, Alabama, USA.
FAU - Hidalgo, Bertha
AU  - Hidalgo B
AD  - Department of Epidemiology, School of Public Health, University of Alabama, 
      Birmingham, Alabama, USA.
FAU - Neuhouser, Marian L
AU  - Neuhouser ML
AD  - Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
FAU - Di, Chongzhi
AU  - Di C
AD  - Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
FAU - Tucker, Katherine L
AU  - Tucker KL
AD  - Department of Clinical Laboratory &Nutritional Sciences, University of 
      Massachusetts Lowell, Massachusetts, USA.
FAU - Arnett, Donna K
AU  - Arnett DK
AD  - Department of Epidemiology, School of Public Health, University of Alabama, 
      Birmingham, Alabama, USA.
FAU - Ordovas, Jose M
AU  - Ordovas JM
AD  - Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research 
      Center on Aging, Tufts University, Boston, MA, USA.
AD  - Department of Epidemiology and Population Genetics, Centro Nacional Investigacion 
      Cardiovasculares (CNIC), Madrid, Spain.
AD  - Instituto Madrileno de Estudios Avanzados en Alimentacion, Madrid, Spain.
FAU - Corella, Dolores
AU  - Corella D
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 
      Madrid, Spain.
AD  - Department of Preventive Medicine and Public Health, School of Medicine, 
      University of Valencia, Valencia, Spain.
LA  - eng
GR  - P50 HL105185/HL/NHLBI NIH HHS/United States
GR  - P01 AG023394/AG/NIA NIH HHS/United States
GR  - HHSN268201100001I/HL/NHLBI NIH HHS/United States
GR  - R01 HL091357/HL/NHLBI NIH HHS/United States
GR  - HHSN268201100004I/HL/NHLBI NIH HHS/United States
GR  - HHSN268201100046C/HL/NHLBI NIH HHS/United States
GR  - HHSN268201100003C/WH/WHI NIH HHS/United States
GR  - R01 HL078885/HL/NHLBI NIH HHS/United States
GR  - N02HL64278/HL/NHLBI NIH HHS/United States
GR  - U01 HL072524/HL/NHLBI NIH HHS/United States
GR  - HHSN268201100002C/WH/WHI NIH HHS/United States
GR  - HHSN268201100002I/HL/NHLBI NIH HHS/United States
GR  - R01 HL054776/HL/NHLBI NIH HHS/United States
GR  - HHSN268201100001C/WH/WHI NIH HHS/United States
GR  - N01WH22110/WH/WHI NIH HHS/United States
GR  - K08 HL112845/HL/NHLBI NIH HHS/United States
GR  - HHSN268201100004C/WH/WHI NIH HHS/United States
GR  - N01WH24152/WH/WHI NIH HHS/United States
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GR  - N01WH32105/HL/NHLBI NIH HHS/United States
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GR  - N01WH32108/WH/WHI NIH HHS/United States
GR  - N01WH32109/WH/WHI NIH HHS/United States
GR  - N01WH32111/WH/WHI NIH HHS/United States
GR  - N01WH32112/WH/WHI NIH HHS/United States
GR  - N01WH32113/WH/WHI NIH HHS/United States
GR  - N01 WH32115/WH/WHI NIH HHS/United States
GR  - N01WH32118/HL/NHLBI NIH HHS/United States
GR  - N01WH32119/WH/WHI NIH HHS/United States
GR  - N01WH32122/WH/WHI NIH HHS/United States
GR  - N01WH42107/HL/NHLBI NIH HHS/United States
GR  - N01WH42108/WH/WHI NIH HHS/United States
GR  - N01WH42109/WH/WHI NIH HHS/United States
GR  - N01WH42110/WH/WHI NIH HHS/United States
GR  - N01WH42111/HL/NHLBI NIH HHS/United States
GR  - N01WH42113/WH/WHI NIH HHS/United States
GR  - N01 WH42114/HL/NHLBI NIH HHS/United States
GR  - N01WH42115/WH/WHI NIH HHS/United States
GR  - N01WH42117/WH/WHI NIH HHS/United States
GR  - N01WH42118/HL/NHLBI NIH HHS/United States
GR  - N01WH42119/WH/WHI NIH HHS/United States
GR  - N01WH42120/HL/NHLBI NIH HHS/United States
GR  - N01WH42121/WH/WHI NIH HHS/United States
GR  - N01WH42122/WH/WHI NIH HHS/United States
GR  - N01WH42123/WH/WHI NIH HHS/United States
GR  - N01 WH42124/OD/NIH HHS/United States
GR  - N01WH42125/WH/WHI NIH HHS/United States
GR  - N01WH42126/HL/NHLBI NIH HHS/United States
GR  - N01WH42129/WH/WHI NIH HHS/United States
GR  - N01WH42130/HL/NHLBI NIH HHS/United States
GR  - N01WH42131/HL/NHLBI NIH HHS/United States
GR  - N01WH42132/WH/WHI NIH HHS/United States
GR  - N01WH44221/WH/WHI NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20160914
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Genetic Markers)
RN  - EC 3.6.4.12 (MCM6 protein, human)
RN  - EC 3.6.4.12 (Minichromosome Maintenance Complex Component 6)
SB  - IM
MH  - Aged
MH  - *Alleles
MH  - Animals
MH  - *Cardiovascular Diseases/genetics/mortality
MH  - *Diet, Mediterranean
MH  - Female
MH  - Genetic Markers
MH  - Humans
MH  - Male
MH  - Mediterranean Region
MH  - *Mendelian Randomization Analysis
MH  - Middle Aged
MH  - *Milk
MH  - Minichromosome Maintenance Complex Component 6/*genetics
MH  - Sex Factors
MH  - United States
PMC - PMC5021998
COIS- ER is a non-paid member of the Scientific Advisory Committee of the California 
      Walnut Commission, Sacramento, CA. The other authors declare no competing 
      financial interests.
EDAT- 2016/09/15 06:00
MHDA- 2018/06/01 06:00
PMCR- 2016/09/14
CRDT- 2016/09/15 06:00
PHST- 2016/01/06 00:00 [received]
PHST- 2016/08/23 00:00 [accepted]
PHST- 2016/09/15 06:00 [entrez]
PHST- 2016/09/15 06:00 [pubmed]
PHST- 2018/06/01 06:00 [medline]
PHST- 2016/09/14 00:00 [pmc-release]
AID - srep33188 [pii]
AID - 10.1038/srep33188 [doi]
PST - epublish
SO  - Sci Rep. 2016 Sep 14;6:33188. doi: 10.1038/srep33188.