Background:  Mannose-binding lectin protein coded by MBL2 gene, is associated with the innate immune response during an infection. We hypothesized that genetic variants of MBL2 resulting in production of lower or non-functional protein would be associated with susceptibility to HIV infection and disease progression. This study examined the effects of MBL2 genetic variants on HIV disease in children in the United States.

Methods:  We evaluated for MBL2 polymorphisms, using real-time polymerase chain reaction (PCR), 1058 HIV-infected children aged 42 days to 18 years from PACTG protocols 152 and 300 who received either zidovudine (ZDV), didanosine (ddI), ZDV/ddI or ZDV/lamivudine (3TC) therapy. MBL2 alleles, including wild type (A allele), 230G/A (B allele), 239G/A (C allele), 223C/T (D allele) were studied. The MBL2-A/B/C/D alleles were defined as A/A (wild type homozygote), A/O (heterozygote including A/B, A/C, A/D genotypes) and O/O (homozygous variant including B/B, B/C, B/D, C/C, C/D, D/D genotypes).  

Results:  MBL2-O allele was found in 26.8% of non-Hispanic blacks, 24.9% of Hispanics, and the 20.9% of non-Hispanic whites (p = 0.13). Interestingly, the homozygous C/C genotype was found exclusively in non-Hispanic blacks. Although the presence of MBL2-B/C/D genetic variants (A/O and O/O genotypes) was associated with a somewhat higher relative hazard (RH) for disease progression in children, unlike what has been observed in adults, trends were not statistically significant (O/O vs A/O: RH = 1.8, 95%CI 83 to 3.75, p = 0.14; O/O vs A/A: RH = 1.6, 95%CI 78 to 3.27, p = 0.20; A/O vs. A/A: RH = 0.98, 95%CI 65 to 1.47, p = 0.92). No such trends were observed for the association of MBL2-O allele with the HIV-related central nervous system impairment (p = 0.33).

Conclusions:  Our results to date, do not confirm the finding in adults that MBL2-B/C/D genetic variants (O allele, associated with low MBL2 expression) affect HIV-1 disease progression. Further studies of MBL2 genotypes and haplotypes including H/L, P/Q, X/Y alleles will be required to understand the potential role of MBL2 genetic variants on HIV-1 disease in children.