Department of Cardiovascular, Endocrine and Metabolic Diseases, IRCCS Casa Sollievo della Sofferenza,San Giovanni Rotondo, Italy.
Nephrol Dial Transplant. 2011 Dec;26(12):4011-6. doi: 10.1093/ndt/gfr187. Epub 2011 Apr 14.
Insulin resistance has a role in diabetic nephropathy. The A12 variant of the PPARγ2 P121A polymorphism has been firmly associated with reduced risk of insulin resistance, while its role on the risk of albuminuria in patients with type 2 diabetes is uncertain. This study investigated whether the PPARγ2 P12A polymorphism modulates the risk of albuminuria in these patients.
We tested the association between the A12 variant and albuminuria in three new case-control studies in diabetic patients from Italy (n = 841, n = 623 and n = 714 patients, respectively) and then performed a meta-analysis of all studies available to date. The nine studies we meta-analysed (six previously published and three presented here) comprised a total of 2376 cases and 4188 controls.
In none of the three new studies was a significant association observed with odds ratio (OR) [95% confidence intervals (95% CI)] being 1.115, 0.799 and 0.849 (P = 0.603, 0.358 and 0.518, respectively). At meta-analysis, the overall OR (95% CI) for association between A12 and albuminuria was 0.694 (0.528-0.912). A significant heterogeneity of the genetic effect was observed (P = 0.026), which was totally explained by the different method of urine collection and albuminuria definition utilized across the studies. In fact, most of the effect was observed in the four studies determining albumin excretion rate rather than in those using albumin concentration in a single spot (OR, 95% CI: 0.529, 0.397-0.706, P = 0.0000164 and 0.919, 0.733-1.153, P = 0.47, respectively).
The present study shows that the PPARγ2 Ala12 variant is significantly associated with a reduced risk of albuminuria among patients with type 2 diabetes.
胰岛素抵抗在糖尿病肾病中起作用。PPARγ2 P121A 多态性的 A12 变体与胰岛素抵抗风险降低密切相关，而其在 2 型糖尿病患者白蛋白尿风险中的作用尚不确定。本研究旨在探讨 PPARγ2 P12A 多态性是否调节这些患者的白蛋白尿风险。
我们在来自意大利的 3 项新的病例对照研究中检测了 A12 变体与白蛋白尿之间的关联（分别为 841、623 和 714 例患者），然后对迄今为止所有可用的研究进行了荟萃分析。我们荟萃分析的 9 项研究（包括 6 项已发表的研究和 3 项在此提出的研究）共纳入 2376 例病例和 4188 例对照。
在这 3 项新研究中，没有观察到与比值比（OR）[95%置信区间（95%CI）]的显著关联（OR 值分别为 1.115、0.799 和 0.849，P=0.603、0.358 和 0.518）。荟萃分析中，A12 与白蛋白尿之间的总体 OR（95%CI）为 0.694（0.528-0.912）。观察到遗传效应存在显著异质性（P=0.026），这完全可以通过研究中使用的尿液收集和白蛋白尿定义方法的不同来解释。事实上，大部分影响出现在四项确定白蛋白排泄率而非单次点白蛋白浓度的研究中（OR，95%CI：0.529，0.397-0.706，P=0.0000164 和 0.919，0.733-1.153，P=0.47）。
本研究表明，PPARγ2 Ala12 变体与 2 型糖尿病患者的白蛋白尿风险降低显著相关。
