Abstract
The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death 1) molecule, which negatively regulates self-reactive T- and B-cells in the maintenance of peripheral tolerance. A previous report had shown the development of lupus-like phenotypes in PD-1-deficient C57BL/6 mice, was suggestive to the role of PDCD1 in predisposing to systemic lupus erythematosus (SLE). Hence, we aimed to investigate the association between PDCD1 and SLE susceptibility in the Malaysian population. A TaqMan-based real-time PCR was employed to screen for PD1.1, PD1.3, PD1.5 and PD1.6 in both SLE and healthy control groups of 200 samples each. The observed frequency for PD1.5C/C genotype was significantly higher in Indian SLE patients and Malay controls (p < 0.01). On the other hand, the PD1.5C/T genotype might predispose the Malays to SLE, but confer a protective effect among the Indians (p < 0.01). The PD1.1, PD1.3 and PD1.6 were, however, not correlated to genetic predisposition of SLE in our Malaysian population. In conclusion, PD1.5 variant was significantly associated to SLE susceptibility in our Malaysian cohort. Our failure in replicating the association between other investigated PDCD1 variants and risk of getting SLE might due to ethnic and geographic variations in the distribution of these genetic variants.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease where the dysregulated T-cells activation, over-production of auto-antibodies and accumulation of immune complexes contribute to its phenotypes and complications [1]
Adding to this expanding list, our present study investigated the relationship between the programmed cell death 1 (PDCD1) gene and the development of SLE, which has not yet been reported in our Malaysian population
All the genotypes of these biallelic polymorphisms were reported in our population, except PD1.3 which AA genotype was absent (Table 1)
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease where the dysregulated T-cells activation, over-production of auto-antibodies and accumulation of immune complexes contribute to its phenotypes (e.g., photosensitivity, skin rashes, prolonged fatigue) and complications (e.g., lupus nephritis, coronary artery disease and osteoporosis) [1]. In Malaysia, several potential SLE-predisposing candidate genes involved in immune functions, i.e., genes encode for chemokines, interleukins and their receptors, tumour necrosis factors, T-cell surface receptors, components of the classical complement cascade, as well as major histocompatibility complex have been previously studied [6,7,8,9,10,11,12,13,14,15,16,17] Adding to this expanding list, our present study investigated the relationship between the programmed cell death 1 (PDCD1) gene and the development of SLE, which has not yet been reported in our Malaysian population. This was proven when the C57BL/6-PDCD1−/− mice presented with autoimmune features resembling to SLE, e.g., lupus-like glomerulonephritis with the deposition of IgG3 and C3, arthritis and splenomegaly [21,22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
