Mannose-binding Lectin Gene Polymorphisms and Mycobacterial Lymphadenitis in Young Patients

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Background:Tuberculosis (TB) has recently re-emerged as a major public health threat worldwide. There is strong evidence that host genetic factors influence individual susceptibility to TB and that, once infected, young children and immunocompromised patients are at increased risk for mycobacterial disease and progression to extrapulmonary lymphadenitis.Methods:The association between polymorphisms of mannose-binding lectin and the susceptibility of 139 children with cervical mycobacterial lymphadenitis and infected with Mycobacterium tuberculosis was investigated.Results:The frequencies of genotypes A/B and B/B, based on codon 54 polymorphisms, were significantly different in TB-infected versus healthy control subjects. The frequency of the A/B genotype was significantly lower in TB-infected children (odds ratio = 0.56; 95% confidence interval: 0.36–0.87; P = 0.01), and the B/B genotype was significantly higher in TB-infected children (odds ratio = 4.68; 95% confidence interval: 1.35–16.3; P = 0.01) compared with healthy controls. The HYB haplotype appeared significantly more often to be protective in the healthy control population (odds ratio = 0.23; 95% confidence interval: 0.05–0.96; P = 0.046). Ex vitro phagocytosis assays indicated that high-expression mannose-binding lectin genotypes are associated with an increased risk of infection with M. tuberculosis.Conclusions: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 low-expression genotype A/B and the HYB haplotype may be associated with protection against intracellular mycobacterial infections, whereas the high-expression genotype A/A may confer susceptibility to disease.

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