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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.

Brito EC, Lyssenko V, Renström F, Berglund G, Nilsson PM, Groop L, Franks PW - Diabetes (2009)

Bottom Line: Tests of gene x physical activity interactions on IGR risk for 3 of the 17 polymorphisms were nominally statistically significant:CDKN2A/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.Our observations suggest that the genetic predisposition to hyperglycemia is partially dependent on a person's lifestyle.

View Article: PubMed Central - PubMed

Affiliation: Genetic Epidemiology and Clinical Research Group, Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University Hospital, Umeå, Sweden.

ABSTRACT

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 in 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 on IGR risk for 3 of the 17 polymorphisms were nominally statistically significant:CDKN2A/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.

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Related in: MedlinePlus

Interaction between the HNF1B rs4430796 variant and physical activity on 2-h glucose levels in 8,600 Swedish middle-aged men and women. ■, physically inactive; □, physically active. Data are means adjusted for age and sex. Error bars are 95% CIs. Pinteraction = 0.0009.
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Figure 1: Interaction between the HNF1B rs4430796 variant and physical activity on 2-h glucose levels in 8,600 Swedish middle-aged men and women. ■, physically inactive; □, physically active. Data are means adjusted for age and sex. Error bars are 95% CIs. Pinteraction = 0.0009.

Mentions: The gene × physical activity interaction terms for HNF1B (rs4430796) on IGR risk and on 2-h glucose concentrations were both statistically significant (Pinteraction = 0.026 and 0.0009, respectively), and the latter remained significant after correction for multiple hypothesis testing (Pinteraction = 0.015). Although not statistically significant, the minor A allele at HNF1B rs4430796 tended to be associated with lower risk of IGR (OR 0.92 per allele, 95% CI 0.82–1.03, P = 0.13) in physically inactive individuals (n = 3,335) and with increased risk (1.06, 1.00–1.12, P = 0.066) in physically active individuals (n = 12,015). In a concordant manner, the minor A allele was associated with lower 2-h glucose levels (β = −0.13 mmol/l per allele, P = 0.005) in physically inactive individuals (n = 1,619), with a contrasting effect (0.04, P = 0.056) in physically active individuals (n = 6,981) (Fig. 1). The Cox proportional hazards regression model testing the gene × baseline physical activity interaction term on type 2 diabetes as the outcome yielded an uncorrected P value of 0.0004 (corrected Pinteraction = 0.0068). The nature of the interaction reflected those observed in the glucose regulation models, where the minor allele was associated with decreased risk of diabetes in sedentary individuals (hazard rate ratio [HRR] = 0.85; 95% CI 0.74–0.96; P = 0.011), with a contrasting effect in physically active individuals (HRR = 1.10; 95% CI 1.03–1.18; P = 0.007). To illustrate this interaction, cumulative incidence curves were plotted stratified by genotype and level of physical activity (see Fig. 2).


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.

Brito EC, Lyssenko V, Renström F, Berglund G, Nilsson PM, Groop L, Franks PW - Diabetes (2009)

Interaction between the HNF1B rs4430796 variant and physical activity on 2-h glucose levels in 8,600 Swedish middle-aged men and women. ■, physically inactive; □, physically active. Data are means adjusted for age and sex. Error bars are 95% CIs. Pinteraction = 0.0009.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2682680&req=5

Figure 1: Interaction between the HNF1B rs4430796 variant and physical activity on 2-h glucose levels in 8,600 Swedish middle-aged men and women. ■, physically inactive; □, physically active. Data are means adjusted for age and sex. Error bars are 95% CIs. Pinteraction = 0.0009.
Mentions: The gene × physical activity interaction terms for HNF1B (rs4430796) on IGR risk and on 2-h glucose concentrations were both statistically significant (Pinteraction = 0.026 and 0.0009, respectively), and the latter remained significant after correction for multiple hypothesis testing (Pinteraction = 0.015). Although not statistically significant, the minor A allele at HNF1B rs4430796 tended to be associated with lower risk of IGR (OR 0.92 per allele, 95% CI 0.82–1.03, P = 0.13) in physically inactive individuals (n = 3,335) and with increased risk (1.06, 1.00–1.12, P = 0.066) in physically active individuals (n = 12,015). In a concordant manner, the minor A allele was associated with lower 2-h glucose levels (β = −0.13 mmol/l per allele, P = 0.005) in physically inactive individuals (n = 1,619), with a contrasting effect (0.04, P = 0.056) in physically active individuals (n = 6,981) (Fig. 1). The Cox proportional hazards regression model testing the gene × baseline physical activity interaction term on type 2 diabetes as the outcome yielded an uncorrected P value of 0.0004 (corrected Pinteraction = 0.0068). The nature of the interaction reflected those observed in the glucose regulation models, where the minor allele was associated with decreased risk of diabetes in sedentary individuals (hazard rate ratio [HRR] = 0.85; 95% CI 0.74–0.96; P = 0.011), with a contrasting effect in physically active individuals (HRR = 1.10; 95% CI 1.03–1.18; P = 0.007). To illustrate this interaction, cumulative incidence curves were plotted stratified by genotype and level of physical activity (see Fig. 2).

Bottom Line: Tests of gene x physical activity interactions on IGR risk for 3 of the 17 polymorphisms were nominally statistically significant:CDKN2A/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.Our observations suggest that the genetic predisposition to hyperglycemia is partially dependent on a person's lifestyle.

View Article: PubMed Central - PubMed

Affiliation: Genetic Epidemiology and Clinical Research Group, Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University Hospital, Umeå, Sweden.

ABSTRACT

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 in 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 on IGR risk for 3 of the 17 polymorphisms were nominally statistically significant:CDKN2A/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.

Show MeSH
Related in: MedlinePlus