Abstract
Background: Genetic variants and haplotypes of the interleukin-10 (IL10) gene have been shown to affect clinical outcomes, including the incidence of opportunistic infections (OIs), in HIV-infected patients. This study investigated the effect of IL10 gene variants on susceptibility to OIs in HIV-infected Korean patients in the era of highly active antiretroviral therapy (HAART).Methods: Eighty-five HIV-infected patients receiving HAART were enrolled in the study. OIs were diagnosed based on the published criteria of the Korean Society for AIDS. Three promoter SNPs and four haplotype-tagging SNPs (htSNPs) of IL10 were selected and genotyped. The haplotypes were reconstructed according to the genotyping data and linkage disequilibrium (LD) status of these SNPs.Results: During the study, 38 OIs developed in 23 of the 85 patients (27.1%), at a rate of 1.7 episodes/ patient. Carrying the minor alleles at the rs1518111, rs3024490, and rs1800871 SNPs had a protective effect against OIs (adjusted P=0.035). Among the seven assessed variants, only three possible haplotypes were observed. The second most common haplotype, which was composed of the rs1518111 minor allele and the rs3021094 major allele showed a protective effect against OIs (P=0.0153).Conclusion: This study demonstrated that some IL10 genetic variants and haplotypes are associated with protective effects against OIs in the era of HAART. These data suggest the potential of two htSNPs, rs1518111 and rs3021094, as markers revealing the genetic association of IL10 in Koreans. This is the first report on the association of IL10 with OIs in HIV-infected Korean patients in the era of HAART. (Ann Clin Microbiol 2019;22:14-22)
Keywords
Haplotype HIV IL10 Opportunistic infections Susceptibility
Acknowledgements
This paper was supported by Busan University’s Basic Science Research Program (two year).
Figures & Tables
Fig. 1. Linkage disequilibrium maps of the seven variants in all HIV-infected patients (A), HIV-infected patients with opportunistic infections (B), and HIV-infected patients without opportunistic infections (C). The pairwise D′ and r2 values between pairs of adjacent markers were calculated with Haploview 4.2. The calculated pairwise D′ values of all diamonds were 1, which indicated complete linkage disequilibrium. The number in each diamond is the r2 value, which is shown in a corresponding dark gray-to-white color gradient. Diamonds without a number indicate that the r2 value was 1. No white colored diamonds are shown. Two haplotype tagging SNPs with rs1518111 and 3021094 distinguished each haplotype.
Figures & Tables
Table 1. Demographic and clinical characteristics of patients with and without opportunistic infectionsv
| Characteristics | Total (n=85) | OIs (+) (n=23) | OIs (−) (n=62) | P value |
| Age, y (mean±SD) | 46.9±11.9 | 53.3±11.5 | 44.6±11.2 | 0.002 |
| Age group, n (%) | 0.047 | |||
| ＜40 | 28 (32.9) | 5 (21.7) | 23 (37.1) | |
| 40-60 | 47 (55.3) | 12 (52.2) | 35 (56.5) | |
| ≥60 | 10 (11.8) | 6 (26.1) | 4 (6.5) | |
| Male sex, n (%) | 73 (85.9) | 21 (91.3) | 52 (83.9) | 0.499 |
| CD4 T cell count at initiation of HAART, cell/mm3 (mean±SD) | 165±134 | 94±100 | 196±136 | 0.007 |
| CD4 T cell count after 1 year of HAART, cell/mm3 (mean±SD) | 285±211 | 175±139 | 331±220 | 0.009 |
| Opportunistic infection subtype | ||||
| Tuberculosis, n (%) | 12 (14.1) | 12 (52.2) | ||
| Candidiasis, n (%) | 10 (11.8) | 10 (43.5) | ||
| Pneumocystis jirovecii pneumonia, n (%) | 8 (9.4) | 8 (34.8) | ||
| CMV infection, n (%) | 3 (3.5) | 3 (13.0) | ||
| Cryptococcosis, n (%) | 2 (2.4) | 2 (8.7) | ||
| Other, n (%)* | 3 (3.5) | 3 (13.0) |
