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The Impact of TRAIL (C1595T and G1525A) and DR4 (rs20576) Gene Polymorphisms on Systemic Lupus Erythematosus

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Abstract

Apoptosis dysregulation is a distinct hallmark of several disorders like systemic lupus erythematosus (SLE). In fact, SLE has two special features for apoptosis: irregular apoptosis and decline in clearing of apoptotic bodies. Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) is a death ligand that causes to apoptosis via attaching to its receptors such as death receptor-4 (DR4). The present study aimed to evaluate the effects of TRAIL G1525A and C1595T and DR4 A683C (rs20576) gene polymorphisms on SLE development. 160 SLE patients and 160 healthy individuals as the control group participated in the study. Genotype analysis was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). With regard to TRAIL (C1595T) polymorphism, the frequency of CT genotype was significantly higher in the case group than the control with 3-fold increase in SLE development risk (P = 0.0001). Furthermore, the frequency of the TT genotype also was higher in the case group than the control group with 3.2-fold increase in SLE development risk. The allelic distribution analysis defined the T allele as a risk factor for SLE development (P = 0.0001). The frequency of AA genotype and allele A of TRAIL (G1525A) polymorphism also was statistically higher in the case group than the control group (P = 0.0001). There was no significant association between DR4 rs20576 polymorphism and SLE development. TRAIL C1595T and G1525A gene polymorphisms are suggested as the risk factors for SLE development, although the results showed no association between DR4 rs20576 polymorphism and SLE.

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Acknowledgements

This project was supported by the Research Deputy in Zahedan University of Medical Sciences (IR. ZAUMS. REC.1396.268).

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SS: Methodology and manuscript writing; MS: patient management and designed the experiments; MS: supervision and writing; HS: performed the experiments and analyzed the data. All authors edited and approved the final version submitted for publication.

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Correspondence to Mohsen Saravani.

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We announce that we have no conflict of interest.

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All proceedings performed in the present study containing human participants conform to the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consents were gained from the study subjects. Also, the study protocol was approved by the ethics committee of Zahedan University of Medical Science.

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Sandoughi, M., Salimi, S., Shahraki-Ghadimi, H. et al. The Impact of TRAIL (C1595T and G1525A) and DR4 (rs20576) Gene Polymorphisms on Systemic Lupus Erythematosus. Biochem Genet 58, 649–659 (2020). https://doi.org/10.1007/s10528-020-09966-x

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  • DOI: https://doi.org/10.1007/s10528-020-09966-x

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