Association between Toll-like receptor gene polymorphism and susceptibility to non-human immunodeficiency virus-related cryptococcal meningitis in patients from Fujian Province / 中华传染病杂志

ABSTRACT

Objective:To explore the association between Toll-like receptor (TLR) gene polymorphism and susceptibility to non-human immunodeficiency virus (HIV)-related cryptococcal meningitis in patients from Fujian Province.Methods:A total of 101 non-HIV patients with cryptococcal meningitis and 270 healthy controls in Huashan Hospital, Fudan University and Cangshan Hospital District, The 900th Hospital of the Joint Logistics Support Force from Fujian Province were prospectively enrolled in this case-control study. Genomic DNA was extracted. Genotyping was performed by multiplex SNaPshot technology on eight TLR single nucleotide polymorphism (SNP) which were reported to be related to cryptococcal meningitis but still lacking validations. The differences of gene polymorphism distributions were compared between all patients and healthy controls, and between patients without predisposing factors and healthy controls. Data were analyzed by chi-square test or Fisher exact test.Results:Except for TLR1 rs5743563, the distributions of allele frequency in seven tested TLR SNPs (TLR1 rs5743604, TLR2 rs3804099, TLR4 rs1927907, TLR6 rs3796508, TLR6 rs5743794, TLR9 rs164637 and TLR9 rs352140) were in Hardy-Weinberg equilibrium. Comparisons between cases and controls found that TLR2 rs3804099 T/T genotype (52.5%(53/101) vs 40.4%(109/270), odds ratio ( OR)=1.63, χ2=4.378, P=0.036) and TLR6 rs5743794 G/G genotype (44.6%(45/101) vs 32.2%(87/270), OR=1.69, χ2=4.877, P=0.027) were correlated with high risks of cryptococcal meningitis, while TLR6 rs3796508 G/G genotype ((83.2%(84/101) vs 92.6%(250/270), OR=0.40, χ2=7.271, P=0.007) and TLR9 rs164637 C/C genotype (96.0%(97/101) vs 100.0%(270/270), Fisher exact test , P=0.005) were found to be protective factors. Seventy out of 101 patients had no predisposing factors. Comparison between patients without predisposing factors and healthy controls also found similar results. TLR6 rs5743794 G/G genotype (52.9%(37/70) vs 32.2%(87/270), OR=2.36, χ2=10.216, P=0.001) was risk factor, while TLR6 rs3796508 G/G genotype (81.4%(57/70) vs 92.6%(250/270), OR=0.35, χ2=7.906, P=0.005) and TLR9 rs164637 C/C genotype (97.1%(68/70) vs 100.0%(270/270), Fisher exact test, P=0.042) were protective factors. Conclusion:TLR gene polymorphism is significantly associated with non-HIV-related cryptococcal meningitis, which indicates that TLR might play an important role in the pathogenesis of cryptococcal meningitis.