Natural resistance-associated macrophage protein 1 gene polymorphisms in thalassemia patients with tuberculosis infection
Abstract: that needs regular
blood transfusions leading to accumulation of iron in the cells. This iron
overload level in macrophage might cause intracellular bacteria, particularly
Mycobacterium tuberculosis (MTB) to multiply. Polymorphisms in natural
resistance-associated macrophage protein 1 (NRAMP1), a metal transporter across
the phagosome membrane, play important role in regulating iron, which is also
needed by MTB. Increased iron in thalassemia patients may have an increased
potential risk for TB.
Objective To compare natural resistance-associated macrophage protein 1
(NRAMP1) gene polymorphisms (INT4, D543N, and 3’UTR) in thalassemia patients
with and without tuberculosis (TB) infection.
Methods A cross-sectional measurement of NRAMP1 genetic polymorphisms was
performed in pediatric thalassemia patients with TB (n=40) and without TB
(n=50). Iron status including serum iron, total iron-binding capacity (TIBC), and
ferritin, was compared between the two groups. The NRAMP1 genetic polymorphisms
were analysed using polymerase chain reaction/restriction fragment length
polymorphism (PCR/RFLP). Allelic and genotypic distributions of each
polymorphism were assessed for possible associations with TB infection.
Results Mean serum iron and TIBC in thalassemia patients with TB were
higher compared to thalassemia patients without TB (mean serum: 166.26 vs.
134.92 μmol/L, respectively; P=0.026) and (mean TIBC: 236.78 vs. 195.84 μmol/L,
respectively; P=0.029). In thalassemia patients with TB, we observed
significantly higher frequency of the C allele in INT4 (10% vs. 2%,
respectively; OR=5.44; 95%CI 1.1 to 26.4; P=0.02) and the TGTG deletion allele
(78.8% vs. 51%, respectively; OR=3.56; 95%CI 1.83 to 6.9; P=0.0002) in 3’UTR
polymorphisms than in thalassemia patients without TB. There were no
significant differences in distributions
of the A allele between TB and non-TB groups (16.3% vs. 15%, respectively;
P=0.84) or the GA genotype (32.5% vs. 30%, respectively; P=0.79) in D543N.
Conclusion The NRAMP1 polymorphisms are known to be associated with major
gene susceptibility to TB, and in our thalassemia patients this association is
even more pronounced.
Author: Mohammad Ghozali, Sari
Puspa Dewi, Reni Ghrahani, Ani Melani Maskoen, Lelani Reniarti, Edhyana
Sahiratmadja, Tri Hanggono Achmad
Journal Code: jpkedokterangg160032
