Polymorphisms in human leukocyte antigen (HLA), MBL2, CD209, vitamin D receptor, cytokine, chemokine and chemokine receptor genes have been shown to be associated with development of TB in HIV patients.
No association with tuberculosis was seen with 3 other SLC11A1 loci investigated, which previously have been associated with tuberculosis in other populations or with MBL2 and VDR polymorphisms.
Diplotype LXPA/HYPA, producer of high levels of MBL, was significantly more frequent in HHC than in patients (16.8% vs. 6.4%, P = 0.031) suggesting a protective role against the development of TB disease that has not been previously found.
Several important candidate genes like human leucocyte antigen/alleles and non-human leucocyte antigen genes, such as cytokines and their receptors, chemokines and their receptors, pattern recognition receptors (including toll-like receptors, mannose binding lectin and the dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin), solute carrier family 11A member 1 (formerly known as natural resistance-associated macrophage protein 1) and purinergic P2X7 receptor gene polymorphisms, have been associated with differential susceptibility to TB in various ethnic populations.
It may be hypothesized that heterozygosity for MBL variant alleles, which encodes low serum MBL levels, is associated with protection against clinical tuberculosis.
The results suggest that YA/YA diplotype associated with very high MBL levels may predispose HIV-infected patients to tuberculosis while O/O genotype associated with very low MBL levels may be associated with susceptibility to tuberculosis in HIV uninfected individuals.
The present study suggests that mannose-binding lectin can protect against TB or predispose the host to the disease depending on the haplotype pair of the host.
The role of MBL in human pulmonary disease is less well established, although accumulating evidence suggests that it is a modifier for lung disease in tuberculosis and cystic fibrosis.
Both genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than the healthy control group (P<0.05, OR 1.393, 1.302 and 1.426 respectively).
While this may indicate that high MBL levels protect against infection with TB, the increase was also of a degree consistent with the acute-phase reaction.
Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV- positive patients.
Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV-positive patients.
The protective role of low-producer mbl-2 genotypes against TBC together with the positive correlation observed between non-producer mbl-2 alleles and TBC incidence, suggest a balancing selection: in spite of an increased susceptibility to respiratory infections associated with MBL deficiency, mbl-2 deficient alleles would have been selected along different populations as a consequence of its selective advantage against intracellular pathogens, such as M. tuberculosis.
The distribution of allele and genotype frequencies varied little among the different groups, and it was not possible to establish any clear association between the variants of the MBL2 gene and the susceptibility to or clinical profile of tuberculosis infections in the population analyzed.
Genotype CG at rs7096206 of MBL genes (OR 2.02) and genotype TC at rs6695096 of MASP-2 genes (OR 1.67) were more prevalent in the TB patients than in healthy controls (p<0.05).
In conclusion, MBL2rs1800450 and rs1800451 polymorphisms play a protective role in TB infection and reinforce their critical significance as a potential genetic marker for TB resistance.
The objective of this study is to compare the frequency of TNF-alpha and MBL gene polymorphisms between patients diagnosed with tuberculosis and healthy volunteers in Turkey, and determine the association between tuberculosis and TNF-alpha gene (G308A) and MBL2 gene codon 54 polymorphisms.