Multiple CD59 Polymorphisms in Chinese Patients with Mycobacterium tuberculosis Infection

Abstract

Background and Objective. Tuberculosis (TB) is a major threat to human health, especially in developing countries. Its susceptibility and progression depend on interactions between mycobacterium tuberculosis, host immune system, and genetic and environmental factors. Up to now, many studies have presented the association between TB susceptibility and host genetic polymorphisms, but never regarding CD59 gene, which is an essential complement regulator. This study investigated the relationship between multiple CD59 single nucleotide polymorphisms (SNPs) and susceptibility to TB among Chinese patients. Methods. A case-control study was conducted to investigate the SNPs at CD59 rs1047581, rs7046, rs2231460, rs184251026, rs41275164, rs831633, rs704700, rs41275166, and rs10768024 by sequence-specific primer-polymerase chain reaction (SSP-PCR) in 900 tuberculosis patients and 1,534 controls. Results. The minor allele frequencies at rs2231460, rs184251026, rs41275164, and rs41275166 were extremely low both in the Cases (0.00%-0.61%) and in the Controls (0.07%-0.43%), comparatively at rs1047581, rs7046, rs831633, rs704700, and rs10768024 were notably higher both in the Cases (8.23%-48.39%) and in the Controls (8.57%-47.16%). Among the nine SNPs, only homozygous CC genotype at rs10768024 showed a significant protective effect against TB than homozygous TT genotype (OR(95% CI) = 0.59(0.38, 0.91), χ2 = 5.779, P=0.016), and homozygous TT and heterozygous CT genotypes showed a significant risk of TB infection in the recessive model (OR(95% CI) = 1.68(1.10, 2.56), χ2 = 5.769, P=0.016). Further analysis verified that rs10768024 CC genotype independently related to TB susceptibility (OR(95% CI) = 0.60(0.39, 0.91), Wald χ2 = 5.664, P=0.017) in multivariate logistic regression analysis, and its genetic mutation was independent of the other SNPs (r2 = 0.00-0.20) in haplotype analysis. Conclusions. The first investigation of the CD59 gene and susceptibility to TB suggests a significant risk with homozygous TT and heterozygous CT genotypes at rs10768024 loci. The homozygous CC mutation at rs10768024 loci showed a significant protection against TB susceptibility.