Previously Associated Type 2 Diabetes Variants May Interact With Physical Activity to Modify the Risk of Impaired Glucose Regulation and Type 2 Diabetes A Study of 16,003 Swedish Adults

被引:46
作者
Brito, Ema C. [1 ]
Lyssenko, Valeriya [2 ]
Renstrom, Frida [1 ]
Berglund, Goran [3 ]
Nilsson, Peter M. [3 ]
Groop, Leif [2 ]
Franks, Paul W. [1 ,2 ]
机构
[1] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Med Sect, S-90185 Umea, Sweden
[2] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Clin Res Ctr, Malmo Univ Hosp, Malmo, Sweden
[3] Lund Univ, Dept Med, Malmo Univ Hosp, Malmo, Sweden
关键词
GENOME-WIDE ASSOCIATION; COMMON VARIANTS; LIFE-STYLE; CONFER RISK; GENES; IGF2BP2; TCF7L2; CDKAL1; LOCI; CDKN2A/B;
D O I
10.2337/db08-1623
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE-Recent advances in type 2 diabetes genetics have culminated in the discovery and confirmation of multiple risk variants. Two important, and largely unanswered questions are whether this information can be used to identify individuals most susceptible to the adverse consequences of sedentary behavior and to predict their response to lifestyle intervention; such evidence Would be mechanistically informative and provide a rationale for targeting genetically susceptible subgroups of the population. RESEARCH DESIGN AND METHODS-Gene X physical activity interactions were assessed for 17 polymorphisms ill a prospective population-based cohort of initially nondiabetic middle-aged adults. Outcomes were 1) impaired glucose regulation (IGR) versus normal glucose regulation determined with either fasting or 2-h plasma glucose concentrations (n = 16,003), 2) glucose intolerance (in mmol/l, n = 8,860), or 3) incident, type 2 diabetes (n = 2,063 events). RESULTS-Tests of gene X physical activity interactions oil IGR risk for 3 of the 17 polymorphisms were nominally statistically significant: CDKNT2A/B rs10811661 (P-interaction = 0.015), HNF1B rs4430796 (P-interaction = 0.026), and PPARG rs1801282 (P-interaction = 0.04). Consistent interactions were observed for the CDKN2A/B (P-interaction = 0.013) and HNF1B (P-interaction = 0.0009) variants on 2-h glucose concentrations. Where type 2 diabetes was the outcome, only one statistically significant interaction effect was observed, and this was for the HNF1B rs4430796 variant, (P-interaction = 0.0004). The interaction effects for HNF1B on IGR risk and incident diabetes remained significant after correction for multiple testing (P-interaction = 0.015 and 0.0068, respectively). CONCLUSIONS-Our observations suggest that the genetic predisposition to hyperglycemia is partially dependent on a person's lifestyle. Diabetes 58:1411-1418, 2009
引用
收藏
页码:1411 / 1418
页数:8
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