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Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients.

Choteau L, Vasseur F, Lepretre F, Figeac M, Gower-Rousseau C, Dubuquoy L, Poulain D, Colombel JF, Sendid B, Jawhara S - Sci Rep (2016)

Bottom Line: Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms.The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients.This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U995, F-59000 Lille, France.

ABSTRACT
Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn's disease and this deficiency is frequently associated with a severe Crohn's disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn's disease phenotype in 69 Crohn's disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn's disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.

No MeSH data available.


Related in: MedlinePlus

Association between MBL2 and NOD2 polymorphisms, mannose-binding lectin concentration, functional activity of the MBL-MASP complex and anti-S. cerevisiae antibody levels in Crohn’s disease patients (A–C).Mannose-binding lectin concentration was significantly associated with rs930508 (wild-type C/C heterozygous C/G or homozygous G/G; P < 0.01), rs1800450 (wild-type C/C, heterozygote C/T; P < 0.001) and rs5030737 (wild-type G/G, heterozygote G/A; P < 0.0001) of MBL2 polymorphisms in Crohn’s disease patients. (D) Functional activity of the MBL-MASP complex was significantly associated with the rs5030737 MBL2 polymorphism in Crohn’s disease patients (wild-type G/G, heterozygote G/A; P < 0.05). (E) Relationship between the rs5030737 MBL2 polymorphism and anti-S. cerevisiae antibody levels in Crohn’s disease patients. Anti-S. cerevisiae antibody level was significantly higher in heterozygous Crohn’s disease patients (G/A; n = 9) than in wild-type patients (G/G; n = 60) for the rs5030737 MBL2 variant (P < 0.01). (F) Association between functional activity of the MBL-MASP complex and the NOD2 polymorphism in Crohn’s disease patients. Functional activity of the MBL-MASP1 complex was significantly higher in heterozygous Crohn’s disease patients (C/T; n = 20) when compared to wild-type patients (C/C; n = 50) for the rs2066844 NOD2 variant (P < 0.05).
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f3: Association between MBL2 and NOD2 polymorphisms, mannose-binding lectin concentration, functional activity of the MBL-MASP complex and anti-S. cerevisiae antibody levels in Crohn’s disease patients (A–C).Mannose-binding lectin concentration was significantly associated with rs930508 (wild-type C/C heterozygous C/G or homozygous G/G; P < 0.01), rs1800450 (wild-type C/C, heterozygote C/T; P < 0.001) and rs5030737 (wild-type G/G, heterozygote G/A; P < 0.0001) of MBL2 polymorphisms in Crohn’s disease patients. (D) Functional activity of the MBL-MASP complex was significantly associated with the rs5030737 MBL2 polymorphism in Crohn’s disease patients (wild-type G/G, heterozygote G/A; P < 0.05). (E) Relationship between the rs5030737 MBL2 polymorphism and anti-S. cerevisiae antibody levels in Crohn’s disease patients. Anti-S. cerevisiae antibody level was significantly higher in heterozygous Crohn’s disease patients (G/A; n = 9) than in wild-type patients (G/G; n = 60) for the rs5030737 MBL2 variant (P < 0.01). (F) Association between functional activity of the MBL-MASP complex and the NOD2 polymorphism in Crohn’s disease patients. Functional activity of the MBL-MASP1 complex was significantly higher in heterozygous Crohn’s disease patients (C/T; n = 20) when compared to wild-type patients (C/C; n = 50) for the rs2066844 NOD2 variant (P < 0.05).

Mentions: To explore whether MBL2 polymorphisms are associated with susceptibility to Crohn’s disease and to its clinical and serological manifestations, the MBL2 gene and its promoter were genotyped in 69 Crohn’s disease patients and 30 healthy controls. Two polymorphisms of the MBL2 gene were identified: rs930508 and rs1800450, which were associated with significant mannose-binding lectin deficiency (P < 0.01 and P < 0.0001, respectively; Fig. 3A,B). The polymorphism rs5030737 (codon 52) was associated with a decrease in mannose-binding lectin serum levels (P < 0.0001) and a low level of MBL-MASP functional activity (P < 0.05) in Crohn’s disease patients (Fig. 3C,D). In addition, the polymorphism rs5030737 was associated with significantly increased levels of anti-S. cerevisiae antibodies (P < 0.01) in Crohn’s disease patients (Fig. 3E). In terms of the association between mannose-binding lectin polymorphisms and clinical phenotype of Crohn’s disease, the polymorphism rs5030737 was more common in Crohn’s disease patients with B2 and B3 phenotypes than in those with B1 (Table 1). 13% of Crohn’s disease patients had heterozygous mutations for the rs5030737 variant, which represent 77.7% for B2 and B3 clinical phenotypes vs. 22.3% for B1.


Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients.

Choteau L, Vasseur F, Lepretre F, Figeac M, Gower-Rousseau C, Dubuquoy L, Poulain D, Colombel JF, Sendid B, Jawhara S - Sci Rep (2016)

Association between MBL2 and NOD2 polymorphisms, mannose-binding lectin concentration, functional activity of the MBL-MASP complex and anti-S. cerevisiae antibody levels in Crohn’s disease patients (A–C).Mannose-binding lectin concentration was significantly associated with rs930508 (wild-type C/C heterozygous C/G or homozygous G/G; P < 0.01), rs1800450 (wild-type C/C, heterozygote C/T; P < 0.001) and rs5030737 (wild-type G/G, heterozygote G/A; P < 0.0001) of MBL2 polymorphisms in Crohn’s disease patients. (D) Functional activity of the MBL-MASP complex was significantly associated with the rs5030737 MBL2 polymorphism in Crohn’s disease patients (wild-type G/G, heterozygote G/A; P < 0.05). (E) Relationship between the rs5030737 MBL2 polymorphism and anti-S. cerevisiae antibody levels in Crohn’s disease patients. Anti-S. cerevisiae antibody level was significantly higher in heterozygous Crohn’s disease patients (G/A; n = 9) than in wild-type patients (G/G; n = 60) for the rs5030737 MBL2 variant (P < 0.01). (F) Association between functional activity of the MBL-MASP complex and the NOD2 polymorphism in Crohn’s disease patients. Functional activity of the MBL-MASP1 complex was significantly higher in heterozygous Crohn’s disease patients (C/T; n = 20) when compared to wild-type patients (C/C; n = 50) for the rs2066844 NOD2 variant (P < 0.05).
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4940739&req=5

f3: Association between MBL2 and NOD2 polymorphisms, mannose-binding lectin concentration, functional activity of the MBL-MASP complex and anti-S. cerevisiae antibody levels in Crohn’s disease patients (A–C).Mannose-binding lectin concentration was significantly associated with rs930508 (wild-type C/C heterozygous C/G or homozygous G/G; P < 0.01), rs1800450 (wild-type C/C, heterozygote C/T; P < 0.001) and rs5030737 (wild-type G/G, heterozygote G/A; P < 0.0001) of MBL2 polymorphisms in Crohn’s disease patients. (D) Functional activity of the MBL-MASP complex was significantly associated with the rs5030737 MBL2 polymorphism in Crohn’s disease patients (wild-type G/G, heterozygote G/A; P < 0.05). (E) Relationship between the rs5030737 MBL2 polymorphism and anti-S. cerevisiae antibody levels in Crohn’s disease patients. Anti-S. cerevisiae antibody level was significantly higher in heterozygous Crohn’s disease patients (G/A; n = 9) than in wild-type patients (G/G; n = 60) for the rs5030737 MBL2 variant (P < 0.01). (F) Association between functional activity of the MBL-MASP complex and the NOD2 polymorphism in Crohn’s disease patients. Functional activity of the MBL-MASP1 complex was significantly higher in heterozygous Crohn’s disease patients (C/T; n = 20) when compared to wild-type patients (C/C; n = 50) for the rs2066844 NOD2 variant (P < 0.05).
Mentions: To explore whether MBL2 polymorphisms are associated with susceptibility to Crohn’s disease and to its clinical and serological manifestations, the MBL2 gene and its promoter were genotyped in 69 Crohn’s disease patients and 30 healthy controls. Two polymorphisms of the MBL2 gene were identified: rs930508 and rs1800450, which were associated with significant mannose-binding lectin deficiency (P < 0.01 and P < 0.0001, respectively; Fig. 3A,B). The polymorphism rs5030737 (codon 52) was associated with a decrease in mannose-binding lectin serum levels (P < 0.0001) and a low level of MBL-MASP functional activity (P < 0.05) in Crohn’s disease patients (Fig. 3C,D). In addition, the polymorphism rs5030737 was associated with significantly increased levels of anti-S. cerevisiae antibodies (P < 0.01) in Crohn’s disease patients (Fig. 3E). In terms of the association between mannose-binding lectin polymorphisms and clinical phenotype of Crohn’s disease, the polymorphism rs5030737 was more common in Crohn’s disease patients with B2 and B3 phenotypes than in those with B1 (Table 1). 13% of Crohn’s disease patients had heterozygous mutations for the rs5030737 variant, which represent 77.7% for B2 and B3 clinical phenotypes vs. 22.3% for B1.

Bottom Line: Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms.The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients.This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U995, F-59000 Lille, France.

ABSTRACT
Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn's disease and this deficiency is frequently associated with a severe Crohn's disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn's disease phenotype in 69 Crohn's disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn's disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.

No MeSH data available.


Related in: MedlinePlus