Characteristics of the study population are described in Table . Of the 453 European American participants, those who were HCV RNA negative did not notably differ from those who were HCV RNA positive with regard to age (median: 43 years in each group) or duration of IDU (median: cleared 23 years; chronic, 24 years). Male gender, however, was more common among HCV RNA positive participants (71.8%) compared to those who were HCV RNA negative (62.4%; p = 0.06). In addition, HIV-1 infection was more common among European American participants who were HCV RNA positive (11.9%) compared to those who were HCV RNA negative (4.6%; p = 0.03).
General demographic characteristics of the Urban Health Study population genotyped for common variants in MBL2
Among the 399 African Americans included in this investigation, participants who were HCV RNA negative were similar to those who were HCV RNA positive with regard to age (median: 47 years in each group), duration of IDU (median: cleared 26 years; chronic, 27 years), gender (males: chronic, 61.9%; cleared, 60.7%) and HIV-1 infection (chronic HCV infection, 11.6%; cleared, 9.0%).
HCV RNA and MBL2 genotypes
In separate evaluations of the European American and African American participants who were positive for HCV RNA, genotypic distributions for all fifteen variants were consistent with Hardy-Weinberg proportions (P ≥ 0.05; Table ). Among European American participants, the -289C-containing variant (-289X) of the proximal promoter, which causes MBL deficiency, was over-represented among those who were HCV RNA negative compared to participants who were positive for HCV RNA (OR = 1.65, 95% CI 1.05–2.58). There were no notable associations with the other promoter variants that have been previously shown to alter MBL levels [G618C (H/L) or T65C (P/Q)] or with either structural locus commonly found among European Americans (D or B). Associations with other MBL2 variants did not achieve statistical significance.
Common variants in MBL2 and odds ratio for being HCV RNA negative among injection drug users
In contrast to our observation among European American participants, the -289C (low promoter) genotype was unrelated to HCV RNA status among African American participants (OR, 0.97; P = 0.94). Homozygosity for the C allele of the T-1483C exon 4 polymorphism, which is a synonymous variant without established functional effects, was associated with a two-fold increased likelihood of being HCV negative in the African Americans, but there was no overall association for 1483C carriers (OR, 1.05; 95% CI, 0.62–1.79). HCV clearance among African American participants was not significantly associated with other promoter, structural or intronic variants of MBL2.
HCV RNA and haplotypes of MBL2
Among European Americans, the LXPA haplotype (the only secretor haplotype containing -289C [X]) was associated with an increased likelihood of being negative for HCV RNA when compared to the HYPA haplotype (Table ; OR = 1.73, 95% CI 1.10–2.74; p = 0.01). LXPA is associated with lower MBL levels compared to HYPA. In an additive model, each copy of LXPA was associated with a nearly 2-fold increase in risk (P-trend = 0.01). Among African American participants, there were no significant associations of secretor haplotypes and HCV RNA.
Odds ratio for risk of being HCV RNA negative among European American and African American injection drug users, by MBL2 secretor haplotype profile.
We next examined the relationship between the MBL2
Y/X, A/0 diplotypes and HCV RNA (Table ), comparing participants who carried YA/YA, which has been associated with the highest MBL levels, to participants with other diplotypes in descending order of previously associated serum MBL levels. Among European American participants, those with XA/YO were more likely to be HCV RNA negative (OR, 2.31; 95% CI, 1.07–5.02). Collapsing the diplotypes into four categories based on a previous report of MBL levels [15
], participants in the lowest category (XA/YO and YO/YO) were more likely to be HCV RNA negative than those in the highest category (YA/YA diplotype; OR, 2.00; 95% CI, 1.05–3.82). Participants in intermediate categories were no more likely to be HCV RNA negative than those with the YA/YA diplotype. There were no notable associations of any MBL Y/X, A/0 diplotype and HCV RNA among African American participants (Table ).
MBL2 diplotypes and odds ratio for risk of being HCV RNA negative among injection drug users