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

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  • dc.contributor.author Smith, Caren E.ca
  • dc.contributor.author Fitó Colomer, Montserratca
  • dc.contributor.author Corella, Doloresca
  • dc.date.accessioned 2016-12-05T09:57:23Z
  • dc.date.available 2016-12-05T09:57:23Z
  • dc.date.issued 2016
  • dc.description.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.ca
  • dc.description.sponsorship C. Smith is supported by K08 HL112845. Funding for the individual cohorts is identified below. Boston Puerto Rican Health Study: This study was supported by the National Institutes of Health grants P01 AG023394 and P50 HL105185. GOLDN: This study was supported by National Heart, Lung, and Blood Institute (NHLBI) grant no. U01HL072524 (Genetic and Environmental Determinants of Triglycerides), NHLBI R01 HL091357 (Genomewide Association Study of Lipid Response to Fenofibrate and Dietary Fat), NHLBI grant number HL54776 and HL078885; and by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture, Agriculture Research Service. PREDIMED: This study was funded, by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (projects PI051839, PI070240, PI1001407, G03/140, CIBER 06/03, RD06/0045 PI07-0954, CNIC-06, PI11/02505, SAF2009-12304, AGL2010-22319-C03-03 and PRX14/00527), by the University Jaume I (Project P1-1B2013-54) and by the Generalitat Valenciana (AP111/10, AP-042/11, BEST/2015/087, GVACOMP2011-151, ACOMP/2011/145, ACOMP/2012/190 and ACOMP/2013/159). Dolores Corella thanks the collaboration of the Real Colegio Complutense at Harvard University, Cambridge. MA, USA. WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221 and HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, SN268201100004C. SHARe: Funding for WHI SHARe genotyping was provided by NHLBI Contract N02-HL-64278.The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap through dbGaP accession#6806.
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Smith CE, Coltell O, Sorlí JV, Estruch R, Martínez-González MÁ, Salas-Salvadó J. et al. Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization. Sci Rep. 2016 Sep 14;6:33188. doi: 10.1038/srep33188ca
  • dc.identifier.doi http://dx.doi.org/10.1038/srep33188
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/27695
  • dc.language.iso engca
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Scientific Reports. 2016 Sep 14;6:33188
  • dc.rights © 2016, The Author(s) This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/ca
  • dc.subject.other Sistema cardiovascular -- Malalties -- Aspectes genèticsca
  • dc.subject.other Llet -- Aspectes nutricionalsca
  • dc.title Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization.ca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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