The Association between Mannan‐Binding Lectin Gene Polymorphism and Clinical Leprosy: New Insight into an Old Paradigm

Messias-Reason, Iara José de; Boldt, Angelica Beate Winter; Braga, Anna Carolina Moraes; Stahlke, Ewalda Von Rosen Seeling; Dornelles, Luciana Nasser; Pereira-Ferrari, Lilian; Kremsner, Peter G.; Kun, Jürgen F. J.

doi:10.1086/521627

Cited by 68 publications

(97 citation statements)

References 40 publications

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“…Consistent with previous reports that higher MBL expression is a risk factor for mycobacterial disease, the "high"-expressing haplotype LYPA was also more frequent in patients than in controls (OR, 2.25; P ϭ 0.02, adjusted analysis). There was also a nonsignificant association of this haplotype with lepromatous and borderline leprosy (71). In a second study, Fitness et al analyzed a single exon 1 polymorphism but found no association in Malawi (93).…”

Section: Innate Immune Effector Molecules and Serum Proteinsmentioning

confidence: 98%

“…MBL deficiency was previously correlated with homozygosity or compound heterozygosity for six well-described SNPs of the MBL2 gene: two promoter SNPs (at positions Ϫ550 [H/L] and Ϫ221 [Y/X]), a 5Ј untranslated region SNP (position ϩ4 [P/Q]), and three nonsynonymous SNPs in exon 1 (allele D, R52C; allele B, G54D; and allele C, G57E) (106). These loci are in strong linkage disequilibrium, resulting in only seven common haplotypes from combinations of these six alleles (71,76,106,136).…”

Section: Innate Immune Effector Molecules and Serum Proteinsmentioning

confidence: 99%

“…To date, one of two studies has reported an association between MBL2 gene polymorphisms and clinical leprosy (71). (71).…”

Section: Innate Immune Effector Molecules and Serum Proteinsmentioning

confidence: 99%

“…(71). Haplotypes were identified by the direct sequencing of a single PCR product covering all the variant alleles.…”

Section: Innate Immune Effector Molecules and Serum Proteinsmentioning

confidence: 99%

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Leprosy and the Human Genome

Misch¹,

Berrington²,

Vary

et al. 2010

Microbiol Mol Biol Rev

116

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SUMMARY Despite the availability of effective treatment for several decades, leprosy remains an important medical problem in many regions of the world. Infection with Mycobacterium leprae can produce paucibacillary disease, characterized by well-formed granulomas and a Th1 T-cell response, or multibacillary disease, characterized by poorly organized cellular infiltrates and Th2 cytokines. These diametric immune responses confer states of relative resistance or susceptibility to leprosy, respectively, and have well-defined clinical manifestations. As a result, leprosy provides a unique opportunity to dissect the genetic basis of human in vivo immunity. A series of studies over the past 40 years suggests that host genes influence the risk of leprosy acquisition and the predilection for different clinical forms of the disease. However, a comprehensive, cellular, and molecular view of the genes and variants involved is still being assembled. In this article, we review several decades of human genetic studies of leprosy, including a number of recent investigations. We emphasize genetic analyses that are validated by the replication of the same phenotype in independent studies or supported by functional experiments demonstrating biological mechanisms of action for specific polymorphisms. Identifying and functionally exploring the genetic and immunological factors that underlie human susceptibility to leprosy have yielded important insights into M. leprae pathogenesis and are likely to advance our understanding of the immune response to other pathogenic mycobacteria. This knowledge may inform new treatment or vaccine strategies for leprosy or tuberculosis.

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Section: Innate Immune Effector Molecules and Serum Proteinsmentioning

confidence: 98%

Section: Innate Immune Effector Molecules and Serum Proteinsmentioning

confidence: 99%

“…To date, one of two studies has reported an association between MBL2 gene polymorphisms and clinical leprosy (71). (71).…”

Section: Innate Immune Effector Molecules and Serum Proteinsmentioning

confidence: 99%

“…(71). Haplotypes were identified by the direct sequencing of a single PCR product covering all the variant alleles.…”

Section: Innate Immune Effector Molecules and Serum Proteinsmentioning

confidence: 99%

See 2 more Smart Citations

Leprosy and the Human Genome

Misch¹,

Berrington²,

Vary

et al. 2010

Microbiol Mol Biol Rev

116

View full text Add to dashboard Cite

show abstract

“…Interestingly, the same polymorphisms mediate a certain level of protection against mycobacterial infections with M. tuberculosis and M. leprae [17,18]. Th e reason being that the bacteria, which are covered with MBL are more easily taken up by macrophages which is their preferred host cell.…”

Section: The Serum Proteins Mannose-binding Lectin and Fi Colin-2 In mentioning

confidence: 99%

Interplay of host and infectious agents

Ouf

Bechlars

Böttger

et al. 2010

Wien Klin Wochenschr

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In this group we would like to answer the question why people show a different response against certain pathogens. In many infections the course of the disease can range from asymptomatic carriage to the severest forms even death. In the past we have analysed candidate genes and their role in the course of malaria and could detect some polymorphisms influencing infectious diseases in the genes encoding NOS2, MBL2, IFNa, FCN2, and receptors for IFNg and IFNa. Having worked initially mainly on malaria we broadened our spectrum also to other infectious diseases like hepatitis B, Leprosy, schistosomiasis. Here we give a short overview about ongoing projects.

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The +3187A/G HLA‐G polymorphic site is associated with polar forms and reactive reaction in leprosy

Lucena‐Silva

Teixeira

Ramos

et al. 2013

Molec Gen & Gen Med

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Considering that variability in immune response genes has been associated with susceptibility to leprosy and with disease severity, leprosy presents clinicopathological variants that are highly associated with the immune response, HLA-G has a well-recognized role in the modulation of the immune response, and polymorphisms at the 3′ untranslated region (UTR) of the HLA-G gene may influence HLA-G production, we studied the polymorphic sites at the 3′ UTR of the HLA-G gene in leprosy and their association with disease severity. We evaluated by sequencing analysis the allele, genotype, and haplotype frequencies of the 3′ UTR HLA-G polymorphic sites (14-bpINDEL/+3003C-T/+3010C-G/+3027A-C/+3035C-T/+3142C-G/+3187A-G/+3196C-G) in 146 individuals presenting reactive leprosy from a highly endemic area, and associated with bacillary load and the type of reactive leprosy. A total of 128 healthy subjects were also studied. Allele, genotype, and haplotype frequencies for the 3′ UTR HLA-G polymorphisms in leprosy patients did not differ from those observed in healthy donors. The +3187A allele was responsible for protection against the development of multibacillary leprosy in a dominant model (AA + AG)/GG, OR = 0.11, P = 0.018), and the +3187A allele and +3187A-A genotype were overrepresented in type II reactive leprosy reaction. The effect of genetic factors on leprosy susceptibility may be hidden by environmental components in highly endemic areas. The HLA-G + 3187A polymorphic site, which is related to unstable mRNA production, was associated with the development of polar forms of leprosy and reactive leprosy reaction.

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The Association between Mannan‐Binding Lectin Gene Polymorphism and Clinical Leprosy: New Insight into an Old Paradigm

Abstract: These results suggest that MBL2-gene polymorphisms play a role in susceptibility to leprosy per se and in the clinical progression of the disease.

Cited by 68 publications

References 40 publications

Leprosy and the Human Genome

Leprosy and the Human Genome

Interplay of host and infectious agents

The +3187A/G HLA‐G polymorphic site is associated with polar forms and reactive reaction in leprosy

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