Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program

被引：92

作者：

Delahanty, Linda M. ^{[2
,3
]}

Pan, Qing ^{[4
]}

Jablonski, Icatiileen A. ^{[4
]}

Watson, Karol E. ^{[5
]}

McCaffery, Jeanne M. ^{[6
,7
]}

Shuldiner, Alan ^{[8
,9
]}

Kahn, Steven E. ^{[10
,11
]}

Knowler, William C. ^{[12
]}

Florez, Jose C. ^{[2
,3
,13
,14
]}

Franks, Paul W. ^{[1
,15
]}

机构：

[1] Lund Univ, Skane Univ Hosp, Ctr Diabet, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden

[2] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[4] George Washington Univ, Ctr Biostat, Rockville, MD USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[6] Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA

[7] Brown Med Sch, Providence, RI USA

[8] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[9] Univ Maryland, Sch Med, Program Genet & Genom Med, Baltimore, MD 21201 USA

[10] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA

[11] Univ Washington, Seattle, WA 98195 USA

[12] NIDDK, Phoenix, AZ USA

[13] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA

[14] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[15] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

来源：

DIABETES CARE | 2012年 / 35卷 / 02期

基金：

瑞典研究理事会; 美国国家卫生研究院;

关键词：

INTERVENTION; RECEPTOR;

D O I：

10.2337/dc11-1328

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：363 / 366

页数：4

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