Tejeda Christina, Broadaway Alaine K, Ombrello Michael J, Brown Milton R, Ponder Lori A, Pichavant Mina Rohani, Wang Gabriel, Angeles-Han Sheila, Hersh Aimee, Bohnsack John, Conneely Karen N, Epstein Michael, Prahalad Sampath
Department of Pediatrics Emory University School of Medicine, Atlanta. United States.
Department of Human Genetics, Emory University School of Medicine, Atlanta. United States.
Curr Rheumatol Rev. 2017;13(3):219-223. doi: 10.2174/1573397113666170104123113.
Variants in the gene encoding Programmed Cell Death-1 (PDCD1) have been associated with susceptibility to Systemic Lupus Erythematosus and other autoimmune diseases. Given that clinically distinct autoimmune phenotypes share common genetic susceptibility factors, variants in PDCD-1 were tested for a possible association with Juvenile Idiopathic Arthritis (JIA).
Four Single Nucleotide Polymorphisms (SNPS) in the PDCD1 gene were genotyped and analyzed: rs7421861, rs11568821, rs10204525, and rs7568402 in 834 cases and 855 controls of Northern European ancestry. Each variant was examined for possible associations with JIA and then analyzed for association with JIA categories.
PDCD1 variants showed no association with JIA in the cohort overall (rs7421861 p=0.63, rs11568821 p=0.13, rs10204525 p=0.31, and rs7568402 p=0.45). Stratification by JIA categories indicated a significant association between systemic JIA and PDCD1 rs7568402 (OR=0.53, p=0.0027), which remained significant after 10,000 permutations, but was not replicated in an independent multi-ethnic systemic JIA cohort. A nominal association between enthesitis-related arthritis and rs115668821 was also observed (OR=0.22, p=0.012).
Unlike other multiple autoimmune disease associated genetic variants, there was no association between PDCD1 variants and JIA or JIA categories.
编码程序性细胞死亡蛋白1（PDCD1）的基因变异与系统性红斑狼疮及其他自身免疫性疾病的易感性相关。鉴于临床上不同的自身免疫表型共享常见的遗传易感性因素，对PDCD - 1基因变异与幼年特发性关节炎（JIA）的可能关联进行了检测。
对834例病例和855例北欧血统对照进行了PDCD1基因中的4个单核苷酸多态性（SNP）的基因分型和分析：rs7421861、rs11568821、rs10204525和rs7568402。检测每个变异与JIA的可能关联，然后分析其与JIA分类的关联。
在整个队列中，PDCD1变异与JIA无关联（rs7421861 p = 0.63，rs11568821 p = 0.13，rs10204525 p = 0.31，rs7568402 p = 0.45）。按JIA分类分层显示，全身型JIA与PDCD1 rs7568402之间存在显著关联（OR = 0.53，p = 0.0027），经10000次置换后仍显著，但在独立的多民族全身型JIA队列中未得到重复验证。还观察到附着点炎相关关节炎与rs115668821之间存在名义上的关联（OR = 0.22，p = 0.012）。
与其他多种自身免疫性疾病相关的基因变异不同，PDCD1变异与JIA或JIA分类之间无关联。
