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PLoS Med. 2011 Oct;8(10):e1001106. doi: 10.1371/journal.pmed.1001106. Epub 2011 Oct 11.

The effect of chromosome 9p21 variants on cardiovascular disease may be modified by dietary intake: evidence from a case/control and a prospective study.

Collaborators (411)

Diaz R, Paolasso E, Ciruzzi M, Nordaby R, Sosa CH, Luciardi HL, Marzetti EM, Piasentin JA, Muchastegui M, Cuneo C, Zapata G, Bono JO, Marxetti EM, Caccavo A, Guerrero RA, Nordaby R, Dizeo C, Hunt D, Varigos J, Sallaberger M, Aroney G, Hicks P, Campbell D, Amerena J, Walsh W, Nelson G, Careless D, Durech J, Gunawardane K, Thomson A, Owensby D, Buncle A, Watson B, Ikram H, Audeau M, Hills M, Rosen D, Rankin J, Tunesi A, Sampson J, Roberts K, Hamer A, Roberts L, Singh B, Singh C, Hendriks R, Tulloch G, Hill A, Rees D, Hall C, Halim MA, Khalifa Al, Amin MI, Haque S, Mujih S, Faruque GM, Hossain M, Agboton H, Onen C, Avezum A, Piegas L, Reis G, Esteves JP, Bodanese LC, Junior AR, Neto JA, Ramos RF, Silva ES, Labrunie A, Carvalho AC, Filho IP, Abrantes JA, Gebara OC, Leaes PE, Xavier SS, Marino RL, Dutra O, Muna W, Blackett KN, Yaoundé CH, Teo K, Yusuf S, Ounpuu S, Chan YK, Joyner C, Kitching AD, Morris A, Panju A, Lee H, Bata I, May B, Hiscock JG, Greenwood PV, Tymchak W, Natarajan M, Lanas F, Standen D, Lanas A, Santibanez C, Soto P, Potthoff S, Soto R, Mercadal E, Liu LS, Jiang LX, Chen Q, Sun N, Wang J, Zhang L, Li X, Chen H, Li Z, Shi Y, Meng J, Wang D, Liu Z, Yan J, Zhang W, Wan Z, Xu Y, Li X, Wang L, Fu Q, Zhu K, Wang Y, Wang X, Wang F, Liu R, Zhao R, Sun K, Yue S, Zhang Y, Zhao X, Zhao L, Zhou C, Meng X, Liu A, Li X, Wu R, Xiao R, Zhang X, Wan G, Chen X, Ge Z, Zhou T, Li Y, Zhou X, Zhang F, Bautista LE, Casas JP, Morillo CA, Ardilla E, Arenas IA, Lindarte M, Aristizabal D, Rumboldt Z, Rumboldt M, Carevic V, Widimsky P, Branny M, Gregor P, Khedr MS, Abdel-Aziz MG, Abdel-Kader S, Abdel-Moneim MA, El-Demerdash F, El-Saiid A, Gharib S, Hassanin M, Abdel-Hamid F, Maklady, Sadek I, Rupprecht HJ, Wittlinger T, Schuster P, Schmidt A, Ochs HR, Karatzas N, Pipilis A, Symeonides D, Karidis K, Tsaknakis TH, Kyfnidis K, Luna M, Arroyo AM, Sotomora G, Rodas MA, Velasquez L, Ovando A, Sanderson J, Ma WY, Chan S, Keltai M, Szaboki F, Karpati P, Toth K, Timar S, Kalo E, Janosi A, Rusznak M, Lehoczky D, Tarjan J, Kiss E, Sitkei E, Valyi P, Edes I, Pais P, Reddy KS, Joshi PP, Prabhakaran D, Xavier D, Roy A, Ramakrishnan L, Hasani MR, Mirkhani SH, Halon D, Lewis B, Franzosi MG, Tognoni G, Gardinale E, Villella M, Mennuni M, Saiu F, Pettinati G, Ciricugno S, Antonaci S, Carrieri L, Balli E, Bicego D, DelleDonne MG, Ottaviano A, Moretti L, Melloni C, Melandri G, Carbonieri E, Vetrano A, Hori M, Sato H, Fujii K, Ogola EN, Wangai P, Zubaid M, Rashed W, Lang CC, Ahmad WA, Kadirvelu A, Zambahari R, Ramos-Corrales MA, Damasceno A, Pandey MR, Baniya G, Sayami A, Kiratee M, Rawat B, Pandey M, Gurung J, Peters R, Basart DC, Bronzwaer PN, Heijmeriks JA, Michels HR, Pop GM, Akinroye KK, Kazmi K, Memon NA, Memon SK, Nishtar S, Badar A, Mattu MA, Yakub M, Soomra K, Khatri J, Faruqui AM, Rasool SI, Samad A, Dans AL, Punzalan FQ, Villarruz MV, Mendoza BT, Recto CS 3rd, Tamesis BR, Mendoza V, Torres DJ, Morales DD, Ongtengco I, Budaj A, Ceremuzynski L, Stec S, Gorny J, Prochniewska K, Urbanek TK, Wojewoda P, Pawlowski M, Religa K, Klabisz R, Latocha H, Szpajer M, Cymerman K, Laniec M, Danielewicz H, Ogorek M, Kopcik D, Baranowska A, Kozlowski A, Blachowicz M, Jedrzejowski A, Waszyrowski T, Zielinski Z, Janik K, Tomzynski M, Mytnik M, Maziarz A, Rembelska G, Piepiorka M, Debkowska K, Krynski T, Szczeklik BS, Krasowski W, Rozwodowska M, Miekus P, Surwilo J, Malinowski S, Hybel J, Michalak M, Achremczyk P, Majchrzak J, Korombel WS, Dobrowolski M, Gessek J, Morais J, Gehani AA, Hajar HA, Almowla MM, Omer AA, Volkova EG, Levashov SU, Filatova OM, Evchenko UI, Malkiman GS, Karaulovskaya NN, Panovsky J, Johan BA, Cheng A, Ng KS, Neoh KH, Tan KS, Lum LN, Cheah Y, Commerford P, Steyn K, Brown B, Martiz F, Raubenheimer P, Aboo A, Marx JD, Batiste E, Sliwa K, Sareli P, Zambiakides C, Valentin V, Ferriz J, Rovira A, Rodriguez-Llorian A, Cereijo E, Monzo T, Alonso N, Gomez-Martinez E, Lopez-Perez A, Mendis S, Jayalath T, Hinai AT, Hassan MO, Rosengren A, Sitthi-Amorn C, Chaithiraphan S, Bhuripanyo K, Srimahachota S, Anukulwutipong M, Loothavorn P, Sritara P, Tanomsup S, Tantitham J, Tatsanavivat P, Yipinsoi T, Jintapakorn W, Puavilai W, Koanantakul B, Kasemsuwan P, Supanantareauk C, Peamsomboon C, Saejueng B, Jeamsomboon K, Sukontasup A, Almahmeed W, Abdelwareth LO, Bokhari A, Rao NS, Bakir S, Yusufali AM, Hatou E, Zaidi Q, Fox K, Flather M, Probstfield J, Freeman R, Mathew J, Schweiger M, Johnson W, Ofili E, Chifamba J, Hakim AJ.

Author information

1
Department of Human Genetics, McGill University, Montréal, Quebec, Canada.

Abstract

BACKGROUND:

One of the most robust genetic associations for cardiovascular disease (CVD) is the Chromosome 9p21 region. However, the interaction of this locus with environmental factors has not been extensively explored. We investigated the association of 9p21 with myocardial infarction (MI) in individuals of different ethnicities, and tested for an interaction with environmental factors.

METHODS AND FINDINGS:

We genotyped four 9p21 SNPs in 8,114 individuals from the global INTERHEART study. All four variants were associated with MI, with odds ratios (ORs) of 1.18 to 1.20 (1.85×10(-8)≤p≤5.21×10(-7)). A significant interaction (p = 4.0×10(-4)) was observed between rs2383206 and a factor-analysis-derived "prudent" diet pattern score, for which a major component was raw vegetables. An effect of 9p21 on MI was observed in the group with a low prudent diet score (OR = 1.32, p = 6.82×10(-7)), but the effect was diminished in a step-wise fashion in the medium (OR = 1.17, p = 4.9×10(-3)) and high prudent diet scoring groups (OR = 1.02, p = 0.68) (p = 0.014 for difference). We also analyzed data from 19,129 individuals (including 1,014 incident cases of CVD) from the prospective FINRISK study, which used a closely related dietary variable. In this analysis, the 9p21 risk allele demonstrated a larger effect on CVD risk in the groups with diets low or average for fresh vegetables, fruits, and berries (hazard ratio [HR] = 1.22, p = 3.0×10(-4), and HR = 1.35, p = 4.1×10(-3), respectively) compared to the group with high consumption of these foods (HR = 0.96, p = 0.73) (p = 0.0011 for difference). The combination of the least prudent diet and two copies of the risk allele was associated with a 2-fold increase in risk for MI (OR = 1.98, p = 2.11×10(-9)) in the INTERHEART study and a 1.66-fold increase in risk for CVD in the FINRISK study (HR = 1.66, p = 0.0026).

CONCLUSIONS:

The risk of MI and CVD conferred by Chromosome 9p21 SNPs appears to be modified by a prudent diet high in raw vegetables and fruits. Please see later in the article for the Editors' Summary.

PMID:
22022235
PMCID:
PMC3191151
DOI:
10.1371/journal.pmed.1001106
[Indexed for MEDLINE]
Free PMC Article

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