Ann Clin Microbiol.  2019 Mar;22(1):14-22. 10.5145/ACM.2019.22.1.14.

Genetic Variants and Haplotypes in the IL10 Gene and Their Association with Opportunistic Infections among HIV-Infected Patients in Korea in the Era of Highly Active Antiretroviral Therapy

Affiliations
  • 1Department of Laboratory Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Busan, Korea. iskim0710@gmail.com
  • 2Department of Laboratory Medicine and Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.

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.

Keyword

Haplotype; HIV; IL10; Opportunistic infections; Susceptibility

MeSH Terms

Alleles
Antiretroviral Therapy, Highly Active*
Haplotypes*
HIV
Humans
Incidence
Interleukin-10*
Korea*
Linkage Disequilibrium
Opportunistic Infections*
Polymorphism, Single Nucleotide
Interleukin-10

Figure

  • 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.


Reference

1. Sterne JA, Hernán MA, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study. Lancet. 2005; 366:378–384.
Article
2. Zanoni BC. Update on opportunistic infections in the era of effective antiretroviral therapy. Infect Dis Clin North Am. 2014; 28:501–518.
Article
3. WHO. UNICEF. UNAIDS. Global Update on HIV Treatment 2013: Results, Impact and Opportunities. Geneva: WHO Press;2013.
4. Manosuthi W, Chaovavanich A, Tansuphaswadikul S, Prasithsirikul W, Inthong Y, Chottanapund S, et al. Incidence and risk factors of major opportunistic infections after initiation of antiretroviral therapy among advanced HIV-infected patients in a resource-limited setting. J Infect. 2007; 55:464–469.
Article
5. Kim YJ, Woo JH, Kim MJ, Park DW, Song JY, Kim SW, et al. Opportunistic diseases among HIV-infected patients: a multicenternationwide Korean HIV/AIDS cohort study, 2006 to 2013. Korean J Intern Med. 2016; 31:953–960.
Article
6. Mocroft A, Furrer HJ, Miro JM, Reiss P, Mussini C, Kirk O, et al. The incidence of AIDS-defining illnesses at a current CD4 count ≥200 cells/μL in the post-combination antiretroviral therapy era. Clin Infect Dis. 2013; 57:1038–1047.
7. Naicker DD, Wang B, Losina E, Zupkosky J, Bryan S, Reddy S, et al. Association of IL-10-promoter genetic variants with the rate of CD4 T-cell loss, IL-10 plasma levels, andbreadth of cytotoxic T-cell lymphocyte response during chronic HIV-1 infection. Clin Infect Dis. 2012; 54:294–302.
8. Shrestha S, Wiener HW, Aissani B, Song W, Shendre A, Wilson CM, et al. Interleukin-10 (IL-10) pathway: genetic variants and outcomes of HIV-1 infection in African American adolescents. PLoS One. 2010; 5:e13384.
Article
9. Oleksyk TK, Shrestha S, Truelove AL, Goedert JJ, Donfield SM, Phair J, et al. Extended IL10 haplotypes and their association with HIV progression to AIDS. Genes Immun. 2009; 10:309–322.
Article
10. Erikstrup C, Kallestrup P, Zinyama-Gutsire RB, Gomo E, Butterworth AE, Pedersen BK, et al. Reduced mortality and CD4 cell loss among carriers of the interleukin-10 -1082G allele in a Zimbabwean cohort of HIV-1-infected adults. AIDS. 2007; 21:2283–2291.
Article
11. Wang C, Song W, Lobashevsky E, Wilson CM, Douglas SD, Mytilineos J, et al. Cytokine and chemokine gene polymorphisms among ethnically diverse North Americans with HIV-1 infection. J Acquir Immune Defic Syndr. 2004; 35:446–454.
Article
12. Shin HD, Winkler C, Stephens JC, Bream J, Young H, Goedert JJ, et al. Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. Proc Natl Acad Sci U S A. 2000; 97:14467–14472.
Article
13. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19:683–765.
14. Ho AS. Interleukin-10 and its receptor. Ther Immunol. 1994; 1:173–185.
15. Korean Society for AIDS. The 2013 clinical guidelines for the diagnosis and treatment of HIV/AIDS in HIV-infected Koreans. Infect Chemother. 2013; 45:455–461.
16. Kingkeow D, McNicholl JM, Maneekarn N, Wongtrakul J, Taechareonkul S, Suriyanon V, et al. Frequencies of IL10 SNP genotypes by multiplex PCR-SSP and their association with viral load and CD4 counts in HIV-1-infected Thais. Asian Pac J Allergy Immunol. 2011; 29:94–101.
17. Smolnikova MV. Association of IL2, TNFA, IL4 and IL10 promoter gene polymorphisms with the rate of progression of the HIV infection. Russ J Immunol. 2002; 7:349–356.
18. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, et al. The structure of haplotype blocks in the human genome. Science. 2002; 296:2225–2229.
Article
19. International HapMap Consortium. The International HapMap Project. Nature. 2003; 426:789–796.
20. Jurinke C, van den Boom D, Cantor CR, Köster H. Automated genotyping using the DNA MassArray technology. Methods Mol Biol. 2002; 187:179–192.
Article
21. Phillips MS, Lawrence R, Sachidanandam R, Morris AP, Balding DJ, Donaldson MA, et al. Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots. Nat Genet. 2003; 33:382–387.
Article
22. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005; 21:263–265.
Article
23. Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N, Satorius C, et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease. Nat Genet. 2010; 42:698–702.
Article
24. Vasilescu A, Heath SC, Ivanova R, Hendel H, Do H, Mazoyer A, et al. Genomic analysis of Th1-Th2 cytokine genes in an AIDS cohort: identification of IL4 and IL10 haplotypes associated with the disease progression. Genes Immun. 2003; 4:441–449.
Article
25. Wohl AR, Lu S, Turner J, Kovacs A, Witt M, Squires K, et al. Risk of opportunistic infection in the HAART era among HIV-infected Latinos born in the United States compared to Latinos born in Mexico and Central America. AIDS Patient Care STDS. 2003; 17:267–275.
Article
26. WHO. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. Gevena: WHO press;2013.
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