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Diabetes Care. 2012 Feb;35(2):363-6. doi: 10.2337/dc11-1328. Epub 2011 Dec 16.

Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program.

Collaborators (424)

Bray GA, Culbert IW, Champagne CM, Eberhardt B, Greenway F, Guillory FG, Herbert AA, Jeffirs ML, Kennedy BM, Lovejoy JC, Morris LH, Melancon LE, Ryan D, Sanford DA, Smith KG, Smith LL, St Amant JA, Tulley RT, Vicknair PC, Williamson D, Zachwieja JJ, Polonsky KS, Tobian J, Ehrmann D, Matulik MJ, Clark B, Czech K, DeSandre C, Hilbrich R, McNabb W, Semenske AR, Caro JF, Watson PG, Goldstein BJ, Smith KA, Mendoza J, Liberoni R, Pepe C, Spandorfer J, Donahue RP, Goldberg RB, Prineas R, Rowe P, Calles J, Cassanova-Romero P, Florez HJ, Giannella A, Kirby L, Larreal C, McLymont V, Mendez J, Ojito J, Perry A, Saab P, Haffner SM, Montez MG, Lorenzo C, Martinez A, Hamman RF, Nash PV, Testaverde L, Anderson DR, Ballonoff LB, Bouffard A, Calonge B, Delve L, Farago M, Hill JO, Hoyer SR, Jortberg BT, Lenz D, Miller M, Price DW, Regensteiner JG, Seagle H, Smith CM, Steinke SC, VanDorsten B, Horton ES, Lawton KE, Arky RA, Bryant M, Burke JP, Caballero E, Callaphan KM, Ganda OP, Franklin T, Jackson SD, Jacobsen AM, Kula LM, Kocal M, Malloy MA, Nicosia M, Oldmixon CF, Pan J, Quitingon M, Rubtchinsky S, Seely EW, Schweizer D, Simonson D, Smith F, Solomon CG, Warram J, Kahn SE, Montgomery BK, Fujimoto W, Knopp RH, Lipkin EW, Marr M, Trence D, Kitabchi AE, Murphy ME, Applegate WB, Bryer-Ash M, Frieson SL, Imseis R, Lambeth H, Lichtermann LC, Oktaei H, Rutledge LM, Sherman AR, Smith CM, Soberman JE, Williams-Cleaves B, Metzger BE, Johnson MK, Behrends C, Cook M, Fitzgibbon M, Giles MM, Heard D, Johnson CK, Larsen D, Lowe A, Lyman M, McPherson D, Molitch ME, Pitts T, Reinhart R, Roston S, Schinleber PA, Nathan DM, McKitrick C, Turgeon H, Abbott K, Anderson E, Bissett L, Cagliero E, Florez JC, Delahanty L, Goldman V, Poulos A, Olefsky JM, Carrion-Petersen ML, Barrett-Connor E, Edelman SV, Henry RR, Horne J, Janesch SS, Leos D, Mudaliar S, Polonsky W, Smith J, Vejvoda K, Pi-Sunyer FX, Lee JE, Allison DB, Aronoff NJ, Crandall JP, Foo ST, Pal C, Parkes K, Pena MB, Rooney ES, Van Wye GE, Viscovich KA, Marrero DG, Prince MJ, Kelly SM, Dotson YF, Fineberg ES, Guare JC, Hadden AM, Ignaut JM, Jackson ML, Kirkman MS, Mather KJ, Porter BD, Roach PJ, Rowland ND, Wheeler ML, Ratner RE, Youssef G, Shapiro S, Bavido-Arrage C, Boggs G, Bronsord M, Brown E, Cheatham WW, Cola S, Evans C, Gibbs P, Kellum T, Levatan C, Nair AK, Passaro M, Uwaifo G, Saad MF, Budget M, Jinagouda S, Akbar K, Conzues C, Magpuri P, Ngo K, Rassam A, Waters D, Xapthalamous K, Santiago JV, Dagogo-Jack S, White NH, Das S, Santiago A, Brown A, Fisher E, Hurt E, Jones T, Kerr M, Ryder L, Wernimont C, Saudek CD, Bradley V, Sullivan E, Whittington T, Abbas C, Brancati FL, Clark JM, Charleston JB, Freel J, Horak K, Jiggetts D, Johnson D, Joseph H, Loman K, Mosley H, Rubin RR, Samuels A, Stewart KJ, Williamson P, Schade DS, Adams KS, Johannes C, Atler LF, Boyle PJ, Burge MR, Canady JL, Chai L, Gonzales Y, Hernandez-McGinnis DA, Katz P, King C, Rassam A, Rubinchik S, Senter W, Waters D, Shamoon H, Brown JO, Adorno E, Cox L, Crandall J, Duffy H, Engel S, Friedler A, Howard-Century CJ, Kloiber S, Longchamp N, Martinez H, Pompi D, Scheindlin J, Violino E, Walker E, Wylie-Rosett J, Zimmerman E, Zonszein J, Orchard T, Wing RR, Koenning G, Kramer MK, Barr S, Boraz M, Clifford L, Culyba R, Frazier M, Gilligan R, Harrier S, Harris L, Jeffries S, Kriska A, Manjoo Q, Mullen M, Noel A, Otto A, Semler L, Smith CF, Smith M, Venditti E, Weinzierl V, Williams KV, Wilson T, Arakaki RF, Latimer RW, Baker-Ladao NK, Beddow R, Dias L, Inouye J, Mau MK, Mikami K, Mohideen P, Odom SK, Perry RU, Knowler WC, Cooeyate N, Hoskin MA, Percy CA, Acton KJ, Andre VL, Barber R, Begay S, Bennett PH, Benson MB, Bird EC, Broussard BA, Chavez M, Dacawyma T, Doughty MS, Duncan R, Edgerton C, Ghahate JM, Glass J, Glass M, Gohdes D, Grant W, Hanson RL, Horse E, Ingraham LE, Jackson M, Jay P, Kaskalla RS, Kessler D, Kobus KM, Krakoff J, Manus C, Michaels S, Morgan T, Nashboo Y, Nelson JA, Poirier S, Polczynski E, Reidy M, Roumain J, Rowse D, Sangster S, Sewenemewa J, Tonemah D, Wilson C, Yazzie M, Bain R, Fowler S, Brenneman T, Abebe S, Bamdad J, Callaghan J, Edelstein SL, Gao Y, Grimes KL, Grover N, Haffner L, Jones S, Jones TL, Katz R, Lachin JM, Mucik P, Orlosky R, Rochon J, Sapozhnikova A, Sherif H, Stimpson C, Temprosa M, Walker-Murray F, Marcovina S, Strylewicz G, Aldrich FA, O'Leary D, Stamm E, Rautaharju P, Prineas RJ, Alexander T, Campbell C, Hall S, Li Y, Mills M, Pemberton N, Rautaharju F, Zhang Z, Mayer-Davis E, Moran RR, Ganiats T, David K, Sarkin AJ, Eastman R, Fradkin J, Garfield S, Gregg E, Zhang P, Herman W, Florez JC, Altshuler D, de Bakker PI, Franks PW, Hanson RL, Jablonski K, Knowler WC, McAteer JB, Pollin TI, Shuldiner AR.

Author information

  • 1Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

OBJECTIVE:

We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss-inducing interventions (lifestyle and metformin) versus placebo.

RESEARCH DESIGN AND METHODS:

Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end).

RESULTS:

Irrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (-0.63 and -0.93 kg/allele, P ≤ 0.005, respectively). Gene-treatment interactions were observed for short-term (LYPLAL1 rs2605100, P(lifestyle*SNP) = 0.032; GNPDA2 rs10938397, P(lifestyle*SNP) = 0.016; MTCH2 rs10838738, P(lifestyle*SNP) = 0.022) and long-term (NEGR1 rs2815752, P(metformin*SNP) = 0.028; FTO rs9939609, P(lifestyle*SNP) = 0.044) weight loss. Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (P(lifestyle*SNP) < 0.05).

CONCLUSIONS:

Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.

PMID:
22179955
[PubMed - indexed for MEDLINE]
PMCID:
PMC3263869
Free PMC Article
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