Heterogeneous effect of peroxisome proliferator-activated receptor γ2 Ala12 variant on type 2 diabetes risk
Heterogeneous effect of peroxisome proliferator-activated receptor γ2 Ala12 variant on type 2 diabetes risk
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DOI：
10.1038/oby.2007.617
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发表时间：
2007-05-01
期刊：
影响因子：
6.9
通讯作者：
Trischitta, Vincenzo
中科院分区：
文献类型：
--
作者：
Ludovico, Ornella;Pellegrini, Fabio;Trischitta, Vincenzo
关于PPAR γ 2 Pro12Ala多态性是否在2型糖尿病（T2D）风险中起作用，报道了相互矛盾的结果，表明遗传异质性。为了研究这一问题，我们对41项已发表和2项未发表的研究（共42,910名受试者）进行了荟萃分析。Ala12携带者的T2D风险降低了19%，但这种关联是高度异质性的（p = 0.005）。很大一部分（48%）的异质性可以用对照组的BMI来解释，BMI越低，风险降低的程度越高。亚洲地区Ala12携带者的风险降低率（35%）高于欧洲地区（15%,p = 0.02），并倾向于高于北美地区（18%,p = 0.10）。在调整了对照组的BMI后，亚洲人和欧洲人之间的差异不再显著（p = 0.15）。来自欧洲的研究仍然是异质性的（p = 0.02）， Ala12携带者的风险降低从欧洲北部（26%降低，p < 0.0001）到中部（10%,p = 0.04）和南部（0%,p = 0.94）逐渐减小（优势比趋势检验，p = 0.02）。总之，在我们的荟萃分析中，Ala12携带者的T2D风险降低并不均匀。亚洲的失业率高于欧洲，在欧洲，北欧的失业率更高，中欧几乎不显著，南欧则不存在。
Conflicting results have been reported regarding whether the PPAR gamma 2 Pro12Ala polymorphism plays a role in the risk of type 2 diabetes (T2D), suggesting genetic heterogeneity. To investigate this issue, a meta-analysis of 41 published and 2 unpublished studies (a total of 42,9 10 subjects) was conducted. Ala12 carriers had a 19% T2D risk reduction, but this association was highly heterogeneous (p = 0.005). A great proportion (48%) of heterogeneity was explained by the controls' BMI, with risk reduction being greater when BMI was lower. Risk reduction of Ala12 carriers in Asia (35%) was higher than in Europe (15%, p = 0.02) and tended to be higher than in North America (18%, p = 0.10). Difference between Asians and Europeans was no longer significant (p = 0.15) after adjusting for the controls' BMI. Studies from Europe were still heterogeneous (p = 0.02) with risk reduction in Ala12 carriers being progressively smaller (test for trend in the odds ratios, p = 0.02) from Northern (26% reduction, p < 0.0001) to Central (10%, p = 0.04) and Southern (0%, p = 0.94) Europe. In conclusion, in our meta-analysis, the reduced risk of T2D in Ala12 carriers is not homogeneous. It is greater in Asia than in Europe and, among Europeans, it is higher in Northern Europe, barely significant in Central Europe, and nonexistent in Southern Europe.