Abstract
Background
Previous studies have shown that aberrant T lymphocyte apoptosis is involved in the pathogenesis of uveitis. Genetic variants of apoptotic pathway-related factors (including PDCD1, PDCD1LG2, FAS, and FASLG) may affect apoptosis and in turn predict susceptibility to autoimmune disease. This has not yet been studied in pediatric idiopathic uveitis (PIU) and juvenile idiopathic arthritis (JIA)-associated uveitis and was therefore the subject of the study presented here.
Methods
Fourteen single-nucleotide polymorphisms (SNPs) of several apoptosis-related pathway genes were analyzed in 1238 PIU patients, 128 JIA-associated uveitis patients and 1114 healthy controls using the iPLEX Gold Assay and MassARRAY platform.
Results
A lower frequency of the PDCD1/rs6710479 CC genotype in PIU patients was found when compared to controls (Pc = 3.42 × 10−3). A higher frequency of the PDCD1/rs7421861 A allele (Pc = 4.85 × 10−3) was observed in PIU patients as compared with controls. Stratification analysis showed a positive association of band keratopathy with the PDCD1/rs7565639 CT genotype (Pc = 1.05 × 10−2) and a negative association of this parameter with the PDCD1/rs7565639 C allele (Pc = 3.76 × 10−2).
Conclusions
This study revealed that rs6710479 and rs7421861 in the PDCD1 gene confer susceptibility to PIU in Han Chinese. A stratified analysis showed that PDCD1/rs7565639 is associated with band keratopathy in PIU patients.
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Acknowledgements
We thank all participants involved in the present study. This work was supported by “51282” Project for Henan Medical Science and Technology Innovative Talents, Joint Funds of the National Natural Science Foundation of China U1304812 , Medical Scientific and Technological Project of Henan province 201602092 , Scientific and Technological Project of Henan province 172102310374 , Natural Science Foundation Major International (Regional) Joint Research Project 81720108009, and National Natural Science Foundation Project 81770914.
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T.P. and L.D. made substantial contributions to conception and design. F.L., Q.C., and N.L. made substantial contributions to acquisition of data or analysis and interpretation of data. T.P., Y.L., X.M., and L.S. drafted the article and revised it critically for important intellectual content. P.Y. designed this study. P.Y., A.K., and L.D. gave the final approval of the version to be published. All named authors have agreed to its submission. It is not currently being considered for publication by another journal, and if the paper is accepted it will not subsequently be published in the same or similar form in any language without the consent of publishers.
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Pang, T., Du, L., Li, F. et al. Association of apoptosis genes in PDCD1 but not PDCD1LG2, FAS, and FASLG with pediatric idiopathic uveitis in Han Chinese. Pediatr Res 87, 634–638 (2020). https://doi.org/10.1038/s41390-019-0612-4
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DOI: https://doi.org/10.1038/s41390-019-0612-4
