Transcript The protective compared to other B. Rodés, E-mail: [email protected] role of FUT2 gene in factors associated C.

The protective
compared to other
B. Rodés,
E-mail: [email protected]
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
(428GA) when found on homozygosis is responsible for the nonsecretor 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
428GA 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 nonprogressors and slow-progressors (Table 2).
Table 1: genotypic analysis of FUT2 in LTNP and HIV-negative controls
Gene
Genotype at 428
position
LTNP
( n = 31)
HIV-negative controls
( n = 32)
FUT2
G/G (se+/se+)
7 (22 %)
7 (22 %)
G/A (se+/se-)
16 (52%)
25 (78%)
A/A (se-/se-)
8 (26%)
0
Allele frequency 428A
52 %
39 %
Table 2: viral and host factors associated with non-progression analysed
in the LTNP cohort.
Variable
LTNP
(n = 31)
True Non-progressors (NP) Slow progressors (SP)
(n =15)
(n = 16)
FUT2 phenotype
Non-secretor versus secretor
8 (26%) / 23 (74%)
5 (33%) / 10 (66%)
3 (19%) / 13 (81%)
6 (19%) / 25 (80%)
4 (27%) / 11 (73%)
2 (12%) / 14 (88%)
1 (5%) / 17 (95%)
1 (11%) / 8 (89%)
0 / 9 (100%)
8 (40%) / 12 (60%)
3 (30%) / 7 (70%)
5 (50%) / 5 (50%)
CCR5 genotype
CCR5/D32-CCR5 versus CCR5/CCR5
Nef genotype
DNef versus WT-Nef
Vpr genotype
77Q versus 77R
Conclusions
• There seems to be an association between the nonsense
mutation
428GA
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.