Momin Scherezade, Flores Sylvia, Angel B Bárbara, Codner D Ethel, Carrasco P Elena, Perez-Bravo Francisco
University of Michigan, Ann Arbor, MI, USA.
Diabetes Res Clin Pract. 2009 Mar;83(3):289-94. doi: 10.1016/j.diabres.2008.12.003. Epub 2009 Jan 14.
To explore the contribution of the PD-1 gene polymorphisms involved in T1D as well as the relationship between the PD-1/CTLA-4 genes and soluble CTLA-4 concentrations.
261 incident cases of T1D and 280 healthy children less 15 years old were included in this study. Haplotypes for polymorphisms of the PD-1 and CTLA-4 genes were determined by PCR and RFLP methods. Screening for soluble CTLA-4 was done using an ELISA assay. Statistical analysis was performed using the online SHESIS package.
Our results show that sCTLA-4 levels were higher in T1D than in controls (2.99+/-1.7 ng/ml versus 1.43+/-0.31 ng/ml, p<0.001). The allele dosage of CTLA-4 on PD-1 haplotypes, showing a significant modified effect of G carriers over AA genotype on the sCTLA-4 concentrations (5.48+/-2.09 ng/ml versus 3.27+/-1.30 ng/ml, p<0.03 in T-C haplotype) and (1.92+/-0.79 ng/ml versus 3.41+/-1.10 ng/ml, p<0.02 in C-T haplotype).
Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 is elevated in T1D. Our data suggest a possible gene dosage effect of "G"CTLA-4 carriers on sCTLA-4 over the possible protective or susceptible effect conferred by PD-1 haplotypes.
探讨参与1型糖尿病（T1D）的PD-1基因多态性的作用以及PD-1/CTLA-4基因与可溶性CTLA-4浓度之间的关系。
本研究纳入了261例新发T1D病例和280名15岁以下的健康儿童。采用PCR和RFLP方法确定PD-1和CTLA-4基因多态性的单倍型。使用ELISA检测法筛查可溶性CTLA-4。采用在线SHESIS软件包进行统计分析。
我们的结果显示，T1D患者的可溶性CTLA-4（sCTLA-4）水平高于对照组（2.99±1.7 ng/ml对1.43±0.31 ng/ml，p<0.001）。CTLA-4在PD-1单倍型上的等位基因剂量显示，G携带者相对于AA基因型对sCTLA-4浓度有显著的修饰作用（T-C单倍型中为5.48±2.09 ng/ml对3.27±1.30 ng/ml，p<0.03）以及（C-T单倍型中为1.92±0.79 ng/ml对3.41±1.10 ng/ml，p<0.02）。
与在其他自身免疫性疾病中观察到的较高血清sCTLA-4水平一致，我们的结果表明T1D中sCTLA-4升高。我们的数据表明，“G”CTLA-4携带者对sCTLA-4可能存在基因剂量效应，而不是由PD-1单倍型赋予的可能的保护或易感性效应。
