Autophagy protein 5 (ATG5) rs573775 protects Malaysian Malay women from systemic lupus erythematosus

Objective

Autophagy is one of the critical cellular processes implicated in the pathogenesis of SLE. Polymorphisms in the autophagy-related genes have been associated with increased susceptibility to SLE, particularly variations in the autophagy protein 5 (ATG5) gene which has been associated with SLE in several populations. This case-control study aimed to investigate the association between polymorphisms in ATG5 and SLE in Malaysian population.

Methods

Tetra primer amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to genotype ATG5 rs6937876, rs4945747, rs573775, rs2245214 and rs548234 in 233 SLE patients and 224 healthy controls, collected from 2000 to 2015.

Results

In the overall Malaysian population, AG genotype (adjusted p = 0.013, OR = 1.327, 95 % CI: 1.040 to 1.695) of rs6937876 were significantly associated with increased SLE susceptibility. The dominant model (AG + AA) (adjusted p = 0.006, OR = 0.671, 95 % CI: 0.464 to 0.972), additive model (adjusted p = 0.005, OR = 0.462, 95 % CI: 0.291 to 0.733), and minor A allele (adjusted p = 0.007, OR = 0.628, 95 % CI: 0.447 to 0.882) of rs573775 significantly associated with Malay population by providing protection against SLE.

Conclusion

The SNPs in ATG5 seem to not only conferring SLE susceptibility to the Malaysian population but also protect them from SLE. Gene expression of these SNPs and their interactions with upstream or downstream genes and microenvironment in the Malaysian population, especially Malays, is worth further study.