PPARG2基因Pro12Ala多态性对2型糖尿病风险升高人群中身体活动和久坐时间与胰岛素敏感性标志物之间关联的影响。
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.
作者信息
Yates Thomas, Davies Melanie J, Henson Joseph, Edwardson Charlotte, Webb David, Bodicoat Danielle H, Webb M'Balu, Howard Philip, Cooper Jackie A, Humphries Steve E, Khunti Kamlesh, Talmud Philippa
机构信息
Diabetes Research Centre, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, United Kingdom; National Institute for Health Research (NIHR) Leicester-Loughborough Diet, Lifestyle, and Physical Activity Biomedical Research Unit (BRU), Leicester Diabetes Centre, Leicester, United Kingdom.
Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
出版信息
PLoS One. 2015 May 14;10(5):e0124062. doi: 10.1371/journal.pone.0124062. eCollection 2015.
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.
背景
过氧化物酶体增殖物激活受体γ（PPARγ）是代谢健康的重要调节因子，PPAR-γ2基因（PPARG2）中的一种常见多态性可能会改变生活方式行为与健康之间的关联。
目的
研究PPARG2 Pro12Ala基因型是否会改变久坐行为和中度至剧烈强度身体活动（MVPA）与胰岛素敏感性常用指标之间的关联。
方法
招募葡萄糖调节受损高风险参与者，英国，2010 - 2011年。使用加速度计客观测量久坐时间和MVPA时间。评估空腹及挑战后2小时的胰岛素和葡萄糖水平；使用松田胰岛素敏感性指数（Matsuda-ISI）和稳态模型评估胰岛素抵抗指数（HOMA-IS）计算胰岛素敏感性。从全血中提取DNA。采用线性回归分析久坐时间和MVPA与胰岛素敏感性之间的关联，并按PPARG2 Pro12Ala基因型检验相互作用。
结果
纳入541名受试者（平均年龄 = 65岁，女性 = 33%）；18%携带Ala12等位基因。在调整年龄、性别、种族、药物治疗、吸烟状况和加速度计佩戴时间后，久坐时间和MVPA均与HOMA-IS和Matsuda-ISI密切相关。在进一步相互调整及调整体重指数（BMI）后，仅与Matsuda-ISI的关联得以维持。久坐时间每相差30分钟与Matsuda-ISI相差4%（0，8%；p = 0.043）呈负相关，而MVPA每30分钟与Matsuda-ISI相差13%（0，26%；p = 0.048）呈正相关。MVPA与Matsuda-ISI的关联受基因型影响（p = 0.005），且仅在Ala12等位基因携带者中存在。相反，久坐时间不受基因型影响，在Pro12等位基因纯合子中仍与胰岛素敏感性呈负相关。
结论
PPARG2 Pro12Ala基因型改变了MVPA与Matsuda-ISI之间的关联，仅在18%携带Ala12等位基因的人群中观察到显著关联，而与久坐时间的关联未受影响。
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