The protective compared to other B. Rodés, E-mail: brodes.hciii@salud.madrid.org
role of FUT2 gene in factors associated C. Toro, A. Simón and V. Hospital Carlos III, Madrid, Spain
a cohort of LTNP with Nonprogression Soriano
Background The human FUT2 gene encodes an a(1,2)-fucosyltransferase that regulates the expression of ABH antigens in secretions and mucosa determining the secretor phenotype. The nonsense mutation (428GA) when found on homozygosis is responsible for the non-secretor status1. Recently, the presence of such mutation was associated with slow-progression in HIV-1 infected patients2. In this study we investigate the influence of FUT2 in different groups of long-term non-progresors (LTNP) and its role in protection. References. 1. Koda et al. Leng Med 2001, 3:2-14 2. Kindberg et al. AIDS 2006, 20:685-689.
Patients and Methods A cohort of 31 LTNP with 2 subgroups (15 true non-progressors and 16 slow-progressors, classified according to having a slight CD4 decay overtime or not) was genotyped with respect to the mutation 428GA in the FUT2 gene by automated DNA sequencing using primers described previously2. In addition, 32 HIV-negative controls were also genotyped to see the prevalence of this mutation in our population. Some viral (Nef and Vpr) and host (CCR5D32 genotype) factors had previously been characterized in this LTNP cohort3. References. 3. Rodes et al. AIDS 2004, 18:1109-1116
Results Eight of the 31 LTNP (26 %) were found to be homozygous non-secretors (se-/-) and the rest were secretor positive (74%) (Table 1). The distribution of non-secretors in the two LTNP subgroups was: 5 individuals were true non-progressors (33%) and 3 were slow-progressors (19%). In contrast, the homozygous non-secretor phenotype was not found in the control group. In this group we found 25 heterozygous individuals (Se+/-) (78%) and 7 homozygous (Se+/+) (22%). The CCR5D32 was found in heterozygosis in 19% of the LTNPs (Table 2). Regarding viral factors: 5% of the LTNPs presented a defective Nef and 40% presented the 77Q mutation in Vpr. There were no differences between non-progressors and slow-progressors (Table 2).
Table 1: genotypic analysis of FUT2 in LTNP and HIV-negative controls
Table 2: viral and host factors associated with non-progression analysed in the LTNP cohort.
Conclusions There seems to be an association between the nonsense mutation 428GA observed in the fut2 gene and slow progression, however we did not see differences between true non-progressor patients and slow-progressors. The frequency of the allele 428A in our population is lower than the one reported for other European populations. In our LTNP cohort only FUT2 and Vpr seem to have an effect in non-progression.