The common-866G/A polymorphism in the promoter region of the UCP-2 gene is associated with reduced risk of type 2 diabetes in Caucasians from Italy
The common-866G/A polymorphism in the promoter region of the UCP-2 gene is associated with reduced risk of type 2 diabetes in Caucasians from Italy
复制标题
DOI：
10.1210/jc.2004-1072
复制
发表时间：
2005-02-01
影响因子：
5.8
通讯作者：
Trischitta, V
中科院分区：
文献类型：
--
作者：
Bulotta, A;Ludovico, O;Trischitta, V
解偶联蛋白-2（UCP 2）调节胰岛素分泌，并可能在将肥胖与2型糖尿病（T2 D）联系起来方面发挥重要作用。先前关于UCP 2启动子-866G/A单核苷酸多态性（SNP）在T2 D中的作用的研究给出了相反的结果。我们检测了来自意大利的746名T2 D患者和327名健康无关白种人中-866 G/A SNP的分布。我们还测试了过氧化物酶体增殖物激活受体γ 2（PPARgamma 2）基因的P12 A变体对UCP 2 SNP引起的糖尿病风险的影响。与-866 G/G携带者相比，在-866 G/A和-866 A/A受试者中观察到T2 D风险逐渐降低（P = 0.01），后者显示风险降低约50%[比值比（OR），0.51; 95%置信区间（CI），0.3-0.8; P = 0.003]。相反，-866G/G基因型与风险增加相关（OR，1.31; 95%CI，1.01-1.71）。总体而言，UCP 2 - 866 G/G基因型的人群风险约为12%。在对PPARgamma 2多态性进行分层后，UCP 2 G/G基因型所带来的风险增加在P12/P12纯合子受试者中仍然明显（n = 801; OR，1.38; 95% CI，1.04-1.83），但在X12/A12受试者中似乎消失（即P12/A12杂合子或A12/A12纯合子受试者; n = 137; OR，0.87; 95% CI，0.40-1.91）。这种明显的差异是否完全是由于两种PPARgamma 2基因型携带者数量的不同，这是一个值得深入研究的可能性。总之，在我们的人群中，-866G/A SNP与T2 D相关。需要在更大的样本中进行额外的研究，以调查修饰基因（如PPARgamma 2）的伴随效应的可能性。
Uncoupling protein-2 (UCP2) regulates insulin secretion and may play an important role in linking obesity to type 2 diabetes (T2D). Previous studies of the role of the UCP2 promoter -866G/A single nucleotide polymorphisms (SNP) in T2D have given opposite results. We tested the distribution of the -866G/A SNP in 746 T2D patients and 327 healthy unrelated Caucasians from Italy. We also tested for an effect of the P12A variant of the peroxisomal proliferator-activated receptor-gamma2 (PPARgamma2) gene on diabetes risk given by the UCP2 SNP. Compared with -866G/G carriers, a progressively reduced (P = 0.01) risk of T2D was observed in -866G/A and -866A/A subjects, with the latter showing an approximately 50% risk reduction [odd ratio (OR), 0.51; 95% confidence interval (CI), 0.3-0.8; P = 0.003]. Conversely, the -866G/G genotype was associated with increased risk (OR, 1.31; 95% CI, 1.01-1.71). Overall, the population risk attributable to the UCP2 -866G/G genotype was about 12%. After stratifying for the PPARgamma2 polymorphism, the increased risk conferred by the UCP2 G/G genotype was still evident among P12/P12 homozygous subjects (n = 801; OR, 1.38; 95% CI, 1.04-1.83), but seemed to disappear among the X12/A12 subjects (i.e. P12/A12 heterozygous or A12/A12 homozygous subjects; n = 137; OR, 0.87; 95% CI, 0.40-1.91). Whether this apparent difference is entirely due to the different number of carriers of the two PPARgamma2 genotypes is a likely possibility that deserves deeper investigation. In conclusion, in our population, the -866G/A SNP is associated with T2D. Additional studies in larger samples are needed to investigate the possibility of a concomitant effect of modifier genes such as PPARgamma2.