Division of Dermatology and Cutaneous Sciences, Center for Investigative Dermatology, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
Exp Dermatol. 2011 Jun;20(6):514-9. doi: 10.1111/j.1600-0625.2011.01272.x.
Alterations in the protein tyrosine phosphatase N22 (PTPN22) gene affect the threshold for lymphocyte activation. The PTPN22 1858T polymorphism leads to uninhibited T-cell receptor cascade propagation. An elevated PTPN22 1858C/T genotype frequency has been correlated with several autoimmune disorders which have T-cell and humoral components. However, a recent Tunisian report demonstrated no association between PTPN22 1858T and patients with Pemphigus vulgaris (PV), an autoantibody-associated blistering disorder. Because PTPN22 1858T allele frequency is known to vary across ethnic populations, we conducted a case-control study investigating the relationship between PTPN22 1858T and PV in North American patients of either Ashkenazi Jewish or Caucasian (non-Ashkenazi) decent. Participant genotype was determined in 102 PV patients and 102 healthy controls by restriction fragment length polymorphism-polymerase chain reaction genotyping. Relationships were calculated using Fisher's exact tests and chi-squared tests. We report that the PTPN22 1858C/T genotype is not significantly associated with PV in either Caucasians (P = 0.83) or Ashkenazi Jews (P = 0.60). Further stratification of the patient population by gender, age of disease onset, HLA-type, family history of autoimmune disease, history of anti-desmoglein (anti-Dsg) 3 or anti-Dsg1 antibody response, history of lesion morphology, and disease duration did not uncover significant associations between the PTPN22 1858T allele and PV subgroups. Our data indicate that the PTPN22 1858T mutation is not associated with PV in the North American population. We do observe an elevation of PTPN22 1858C/T genotype frequency in male PV patients. Further investigation will be required to determine if this trend reaches significance in larger studies.
蛋白酪氨酸磷酸酶 N22（PTPN22）基因的改变会影响淋巴细胞激活的阈值。PTPN22 1858T 多态性导致 T 细胞受体级联反应不受抑制地传播。升高的 PTPN22 1858C/T 基因型频率与几种自身免疫性疾病有关，这些疾病具有 T 细胞和体液成分。然而，最近的突尼斯报告表明，PTPN22 1858T 与寻常型天疱疮（PV）患者之间没有关联，PV 是一种自身抗体相关的水疱性疾病。由于 PTPN22 1858T 等位基因频率因种族群体而异，我们进行了一项病例对照研究，调查了北美阿什肯纳兹犹太裔或白种人（非阿什肯纳兹）患者中 PTPN22 1858T 与 PV 之间的关系。通过限制性片段长度多态性-聚合酶链反应基因分型确定了 102 名 PV 患者和 102 名健康对照者的基因型。使用 Fisher 确切检验和卡方检验计算关系。我们报告称，PTPN22 1858C/T 基因型与白种人（P=0.83）或阿什肯纳兹犹太人（P=0.60）中的 PV 均无显著相关性。进一步按性别、疾病发病年龄、HLA 类型、自身免疫性疾病家族史、抗桥粒芯糖蛋白（抗-Dsg）3 或抗-Dsg1 抗体反应史、病变形态史和疾病持续时间对患者人群进行分层，并未发现 PTPN22 1858T 等位基因与 PV 亚组之间存在显著相关性。我们的数据表明，PTPN22 1858T 突变与北美人中的 PV 无关。我们确实观察到男性 PV 患者中 PTPN22 1858C/T 基因型频率升高。需要进一步的研究来确定这种趋势在更大的研究中是否具有统计学意义。
