Effect of the PPARG2 Pro12Ala polymorphism on associations of physical activity and sedentary time with markers of insulin sensitivity in those with an elevated risk of type 2 diabetes
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2015-05-14
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PLoS ONE
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PUBLIC LIBRARY SCIENCE
Melbourne Authors
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General Practice
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Journal Article
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Yates, T., Davies, M. J., Henson, J., Edwardson, C., Webb, D., Bodicoat, D. H., Webb, M., Howard, P., Cooper, J. A., Humphries, S. E., Khunti, K. & Talmud, P. (2015). Effect of the PPARG2 Pro12Ala polymorphism on associations of physical activity and sedentary time with markers of insulin sensitivity in those with an elevated risk of type 2 diabetes. Plos One, 10 (5), https://doi.org/10.1371/journal.pone.0124062.
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Abstract
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is an important regulator of metabolic health and a common polymorphism in the PPAR-γ2 gene (PPARG2) may modify associations between lifestyle behaviour and health. OBJECTIVE: To investigate whether the PPARG2 Pro12Ala genotype modifies the associations of sedentary behaviour and moderate-to-vigorous intensity physical activity (MVPA) with common measures of insulin sensitivity. METHODS: Participants with a high risk of impaired glucose regulation were recruited, United Kingdom, 2010-2011. Sedentary and MVPA time were objectively measured using accelerometers. Fasting and 2-hour post-challenge insulin and glucose were assessed; insulin sensitivity was calculated using Matsuda-ISI and HOMA-IS. DNA was extracted from whole blood. Linear regression examined associations of sedentary time and MVPA with insulin sensitivity and examined interactions by PPARG2 Pro12Ala genotype. RESULTS: 541 subjects were included (average age = 65 years, female = 33%); 18% carried the Ala12 allele. Both sedentary time and MVPA were strongly associated with HOMA-IS and Matsuda-ISI after adjustment for age, sex, ethnicity, medication, smoking status and accelerometer wear time. After further adjustment for each other and BMI, only associations with Matsuda-ISI were maintained. Every 30 minute difference in sedentary time was inversely associated with a 4% (0, 8%; p = 0.043) difference in Matsuda-ISI, whereas every 30 minutes in MVPA was positively associated with a 13% (0, 26%; p = 0.048) difference. The association of MVPA with Matsuda-ISI was modified by genotype (p = 0.005) and only maintained in Ala12 allele carriers. Conversely, sedentary time was not modified by genotype and remained inversely associated with insulin sensitivity in Pro12 allele homozygotes. CONCLUSION: The association of MVPA with Matsuda-ISI was modified by PPARG2 Pro12Ala genotype with significant associations only observed in the 18% of the population who carried the Ala12 allele, whereas associations with sedentary time were unaffected.