Expression of human PTPN22 alleles
Expression of human PTPN22 alleles
复制标题
DOI：
10.1038/sj.gene.6364369
复制
发表时间：
2007-03-01
影响因子：
5
通讯作者：
Lillevang, S. T.
中科院分区：
文献类型：
--
作者：
Nielsen, C.;Barington, T.;Lillevang, S. T.
考虑到与PTPN22 Trp620变异相关的大多数自身免疫性疾病中女性占优势，以及该变异影响免疫耐受的复杂性，本研究的目的是确定与疾病相关的Arg620Trp多态性的等位基因特异性表达是否受到顺式作用或性别特异性反式作用因子/s（如性激素）的影响。对编码1858T多态性的Arg620Trp的等位基因特异性转录物定量分析显示，在妊娠早期和晚期未怀孕女性受试者、男性受试者和怀孕女性受试者的非刺激外周血单个核细胞（PBMCs）中，1858c和t等位基因的表达均无差异（P = 0.70）。激活48 h和72 h后，PTPN22在抗cd3 /抗cd28刺激的PBMCs中的转录分别增加了4倍（P < 0.0001）和13倍（P < 0.0001），而PTPN22 1858c和t等位基因的表达也有相同程度的增加（P = 0.64）。目前的结果基本上排除了这样的现象，即与PTPN22 Trp620变异相关的大多数自身免疫性疾病中女性占优势的部分解释。
Considering the female predominance in most of the autoimmune disorders that associate with the PTPN22 Trp620 variant and the complexity by which this variant influences immunologic tolerance, the objective of this study was to ascertain if the allele-specific expression of the disease-associated Arg620Trp polymorphism is affected by cis-acting or sex-specific trans-acting factor/s (e.g. sex-hormones). The use of the allele-specific transcript quantification of the Arg620Trp encoding 1858T polymorphism revealed no difference in the expression of the 1858C-and T-alleles in non-stimulated peripheral blood mononuclear cells (PBMCs) from non-pregnant female subjects, male subjects or pregnant female subjects in first or third trimester (P = 0.70), respectively. While the transcription of PTPN22 in anti-CD3/anti-CD28 stimulated PBMCs increased fourfold (P < 0.0001) and 13-fold (P < 0.0001) after 48 and 72 h of activation, respectively, the expression of PTPN22 1858C-and T-alleles increased to the same extent (P = 0.64). The present result essentially excludes such phenomena as a partial explanation for the female predominance in most of the autoimmune disorders that associate with the PTPN22 Trp620 variant.