SNPs in PPARG associate with type 2 diabetes and interact with physical activity
SNPs in PPARG associate with type 2 diabetes and interact with physical activity
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DOI：
10.1249/mss.0b013e318159d1cd
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发表时间：
2008-01-01
影响因子：
4.1
通讯作者：
Laakso, Markku
中科院分区：
文献类型：
--
作者：
Kilpelainen, Tuomas O.;Lakka, Timo A.;Laakso, Markku
目的：研究过氧化物酶体增殖物激活受体γ（PPARG）基因7个单核苷酸多态性（SNPs）与糖耐量受损（IGT）向2型糖尿病（T2 D）转化的关系，以及SNPs与体力活动（PA）的相互作用。方法：对参加芬兰糖尿病预防研究（DPS）的超重IGT患者（N = 479）进行随访，平均随访4.2年。每年使用12个月的有效问卷对PA进行评估。结果如下：在考克斯回归分析中，rs 17036314和rs 1801282（Pro 12 Ala）的罕见等位基因预测转化为T2 D（P = 0.03 8和0.03 7，分别），但只有rs 1703 6314预测T2 D校正后的基线空腹血糖（P = 0.030）。按中位数分层的PA总量的变化改变了干预期间rs 17036314和rs 1801282与T2 D风险的相关性（PA变化和基因型之间的相互作用分别为P = 0.002和0.031）; PA的增加似乎消除了风险等位基因的影响。不同的rs 1152003多态性与研究组在转化为T2 D方面相互作用（P = 0.027），并倾向于增加干预组中T2 D的风险（P = 0.050）。未发现rs 1152003与PA变化之间存在相互作用。结论：rs 17036314、rs 1801282（Pro 12 Ala）和rs 1152003与DPS中T2 D的风险相关。PA增加似乎降低了rs 17036314和rs 1801282的风险等位基因对转化为T2 D的影响。rs 1152003的效果被其他生活方式的改变或生活方式的整体干预所改变。
Purpose: To study the associations of seven single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D), and the interactions of the SNPs with physical activity (PA). Methods: Overweight individuals with IGT who participated in the Finnish Diabetes Prevention Study (DPS) (N = 479) were followed, on average, 4.2 yr. PA was assessed yearly with a 12-month validated questionnaire. Results: In Cox regression analyses, the rare alleles of rs 17036314 and rs 1801282 (Pro 12Ala) predicted conversion to T2D (P = 0.03 8 and 0.03 7, respectively), but only rs 1703 6314 predicted T2D after adjustment for baseline fasting glucose (P = 0.030). The change in the total amount of PA, stratified by median, modified the association of rs 17036314 and rs 1801282 with the risk of T2D during the intervention (P = 0.002 and 0.03 1, respectively, for interaction between PA change and genotype); an increase in PA seemed to remove the effect of the risk alleles. The distinct rs 1152003 polymorphism interacted with the study group on the conversion to T2D (P = 0.027) and tended to increase the risk of T2D in the intervention group (P = 0.050). No interaction between rs 1152003 and the change in PA was found. Conclusions: The rs 17036314, rs 1801282 (Pro12Ala), and rs 1152003 were associated with the risk of T2D) in the DPS. Increased PA seemed to decrease the effect of the risk alleles of rs 17036314 and rs 1801282 on the conversion to T2D. The effect of rs 1152003 was modified by other lifestyle changes or the lifestyle intervention as a whole.