IL28B Single-Nucleotide Polymorphism rs12979860 Is Associated With Spontaneous HIV Control in White Subjects

Abstract

The single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene has been associated with the spontaneous clearance of hepatitis C virus. We sought to determine whether this SNP could be associated with the spontaneous control of human immunodeficiency virus (HIV) infection. We studied the prevalence of the IL28B CC genotype among 53 white HIV controllers, compared with the prevalence among 389 HIV-infected noncontrollers. We found that the IL28B CC genotype was independently associated with spontaneous HIV control (odds ratio [OR], 2.669; P = .017), as were female sex (OR, 7.077; P ≤ .001) and the presence of HLA-B57 and/or B27 (OR, 3.080; P = .017). This result supports the idea that common host mechanisms are involved in the spontaneous control of these 2 chronic infections.

Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections

“…This is however different from the dominant model of inheritance seen in HCV studies, [11][12][13]15 suggesting that the two viruses may have different interactions with IFN-λ-driven immune responses. However, unlike in the case of CMV studies discussed above, [47][48][49][50][51] all three HIV studies [72][73][74] show that the minor alleles are non-beneficial, similar to the observations in chronic HCV infections. 15 In summary, it is evident that IFNL SNPs do associate with HIV replication and disease progression, even though in an ethnicity-specific manner.…”

“…[72][73][74] Interestingly, all three studies were carried out on whites/Caucasians, whereas the reports that failed to see an association described above were mostly carried out on African Americans (except that by Rallon et al 69 that used white subjects) or mixed group of blacks and whites. 68 First, Machmach et al 72 found an association of rs12979860 with spontaneous HIV control when tested on 53 white natural viral suppressors and 389 matched non-controllers at P = 0.02 after correcting for occurrence of HLA-B57 (human leukocyte antigen) protective alleles (which also have independent association with HIV and HCV spontaneous clearance) and gender, in multivariate analysis. Second, Machmach et al 73 confirmed and extended their results in another report, where they found the association of rs368234815 with AIDS progression.…”

“…67 A few reports have come up in this area, some showing no correlation of HIV infection/disease progression to the IFNL SNPs, whereas others see clear association. [68][69][70][71][72][73][74] One of the earlier reports tested the association of rs12979860 in 291 high-risk seronegative and 1221 HIV-positive subjects comprising both white and black subjects in the USA. 68 No association was evident for either HIV positivity or for disease progression within the infected subjects.…”

Human leukocyte antigen B*57 does not fully explain hepatitis C clearance in HIV controllers

“…While not observed in all studies [3, 4], most studies suggest a significantly higher rate of spontaneous HCV clearance in HIV controllers (23-39%) [5, 6] than in monoinfected groups (25%) [7] and HIV non-controllers (6.6%-10%) [1, 5]. This has led several groups to examine host genetic factors that might contribute to the control of both virus infections.…”

IFNL4 rs368234815 polymorphism is associated with innate resistance to HIV-1 infection

“…Similar results were observed by Rallon et al [12] in Spaniards and Salgado et al [13] in HIV-1 elite controllers/ suppressors of African American ancestry. On the contrary, Machmach et al [14] studied the prevalence of IFNL4 genotypes (rs12979860) among HIV controllers compared with HIV-1-infected progressors and found that this SNP was associated with spontaneous HIV control. The same group communicated the association of the IFNL4 frameshift variant rs368234815-DG with higher prevalence of AIDS-defining illnesses and lower CD4 lymphocytes levels [15].…”