Marti Amelia, Ochoa M Carmen, Sánchez-Villegas Almudena, Martínez J Alfredo, Martínez-González Miguel Angel, Hebebrand Johannes, Hinney Anke, Vedder Helmut
Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain.
BMC Med Genet. 2006 May 25;7:50. doi: 10.1186/1471-2350-7-50.
Since both excess glucocorticoid secretion and central obesity are clinical features of some obese patients, it is worthwhile to study a possible association of glucocorticoid receptor gene (GRL) variants with obesity. Previous studies have linked the N363S variant of the GRL gene to increased glucocorticoid effects such as higher body fat, a lower lean-body mass and a larger insulin response to dexamethasone. However, contradictory findings have been also reported about the association between this variant and obesity phenotypes. Individual studies may lack statistical power which may result in disparate results. This limitation can be overcome using meta-analytic techniques.
We conducted a meta-analysis to assess the association between the N363S polymorphism of the GRL gene and obesity risk. In addition to published research, we included also our own unpublished data -three novel case-control studies- in the meta-analysis The new case-control studies were conducted in German and Spanish children, adolescents and adults (total number of subjects: 1,117). Genotype was assessed by PCR-RFLP (Tsp509I). The final formal meta-analysis included a total number of 5,909 individuals.
The meta-analysis revealed a higher body mass index (BMI) with an overall estimation of +0.18 kg/m2 (95% CI: +0.004 to +0.35) for homo-/heterozygous carriers of the 363S allele of the GRL gene in comparison to non-carriers. Moreover, differences in pooled BMI were statistically significant and positive when considering one-group studies from the literature in which participants had a BMI below 27 kg/m2 (+ 0.41 kg/m2 [95% CI +0.17 to +0.66]), but the differences in BMI were negative when only our novel data from younger (aged under 45) and normal weight subjects were pooled together (-0.50 kg/m2 [95% CI -0.84 to -0.17]). The overall risk for obesity for homo-/heterozygous carriers of the 363S allele was not statistically significant in the meta-analysis (pooled OR = 1.02; 95% CI: 0.56-1.87).
Although certain genotypic effects could be population-specific, we conclude that there is no compelling evidence that the N363S polymorphism of the GRL gene is associated with either average BMI or obesity risk.
由于糖皮质激素分泌过多和中心性肥胖都是一些肥胖患者的临床特征，因此研究糖皮质激素受体基因（GRL）变异与肥胖之间可能存在的关联是很有意义的。先前的研究已将GRL基因的N363S变异与糖皮质激素作用增强联系起来，如更高的体脂、更低的瘦体重以及对地塞米松更大的胰岛素反应。然而，关于该变异与肥胖表型之间的关联也有相互矛盾的报道。个别研究可能缺乏统计学效力，这可能导致结果不一致。使用荟萃分析技术可以克服这一局限性。
我们进行了一项荟萃分析，以评估GRL基因N363S多态性与肥胖风险之间的关联。除了已发表的研究外，我们还将自己未发表的数据——三项新的病例对照研究——纳入了荟萃分析。这些新的病例对照研究在德国和西班牙的儿童、青少年及成年人中进行（受试者总数：1117名）。通过PCR-RFLP（Tsp509I）评估基因型。最终的正式荟萃分析共纳入了5909名个体。
荟萃分析显示，与非携带者相比，GRL基因363S等位基因的纯合/杂合携带者的体重指数（BMI）总体估计值更高，为+0.18kg/m²（95%置信区间：+0.004至+0.35）。此外，当考虑文献中参与者BMI低于27kg/m²的单组研究时，合并BMI的差异具有统计学意义且为正值（+0.41kg/m²[95%置信区间+0.17至+0.66]），但仅将我们来自较年轻（45岁以下）和正常体重受试者的新数据合并时，BMI差异为负值（-0.50kg/m²[95%置信区间-0.84至-0.17]）。在荟萃分析中，363S等位基因的纯合/杂合携带者患肥胖症的总体风险无统计学意义（合并比值比=1.02；95%置信区间：0.56 - 1.87）。
尽管某些基因型效应可能具有人群特异性，但我们得出结论，没有确凿证据表明GRL基因的N363S多态性与平均BMI或肥胖风险相关。
