Meta-analysis of functional MBL polymorphisms. Associations with rheumatoid arthritis and primary Sjögren's syndrome
1Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, 136-705, Seoul, Korea.
Objective:
The aim of this study was to determine whether functional mannose-binding lectin gene (MBL) polymorphisms are associated with the susceptibility to rheumatoid arthritis (RA) or primary Sjögren's syndrome (pSS).
Methods:
A meta-analysis was conducted to investigate the potential association of RA or pSS with MBL polymorphisms, including the codon 54 (allele B), codon 57 (allele C), and codon 52 (allele D) variants of exon 1, and the - 550 (allele L) and - 221 (allele X) promoter variants.
Results:
A total of 12 comparative studies, including eight RA (1623 patients and 1671 controls) and four pSS (280 patients and 516 controls) studies, were included in the meta-analysis. The meta-analysis revealed no association between the MBL B allele and RA in the overall study population (odds ratio [OR] 0.991, 95 % confidence interval [CI] 0.726-1.355, p = 0.957). However, the meta-analysis showed significant associations between the MBL D, H, and X alleles and RA in the overall population (OR 1.708, 95 % CI 1.077-2.707, p = 0.023; OR 1.936, 95 % CI 1.218-3.078, p = 0.005; OR 1.582, 95 % CI 1.216-2.057, p = 0.001, respectively). An association was found between the MBL B allele and pSS in the overall study population (OR 0.691, 95 % CI 0.541-0.917, p = 0.010). Stratification by ethnicity indicated a trend toward an association between the B allele and pSS in European populations, but no association in Asian populations (OR 0.689, 95 % CI 0.465-1.021, p = 0.063; OR 0.896, 95 % CI 0.311-2.562, p = 0.838, respectively).
Conclusion:
This meta-analysis demonstrated an association between the MBL D, L, and X alleles and the risk of RA. It also demonstrated an association between the MBL B allele and the susceptibility to pSS, suggesting a protective role of the MBL B allele against the development of pSS.
Insights
This meta-analysis found that mannose-binding lectin (MBL) gene polymorphisms D, L, and X are associated with rheumatoid arthritis (RA) risk. The MBL B allele may protect against primary Sjögren's syndrome (pSS) development.
Area of Science:
- Immunogenetics
- Rheumatology
- Autoimmune Diseases
Background:
- Mannose-binding lectin (MBL) plays a crucial role in the innate immune system.
- MBL gene polymorphisms can affect MBL levels and function, potentially influencing autoimmune disease susceptibility.
Purpose of the Study:
- To investigate the association between functional MBL gene polymorphisms and the risk of developing rheumatoid arthritis (RA) or primary Sjögren's syndrome (pSS).
Main Methods:
- A comprehensive meta-analysis was performed on 12 comparative studies.
- The analysis included MBL polymorphisms in exon 1 (alleles B, C, D) and the promoter region (alleles L, X).
- Data from 1623 RA patients and 1671 controls, and 280 pSS patients and 516 controls were analyzed.
Main Results:
- No association was found between the MBL B allele and RA risk.
- Significant associations were observed between MBL alleles D, H, and X and an increased risk of RA.
- The MBL B allele was associated with a reduced risk of pSS, particularly in European populations.
Conclusions:
- Specific MBL gene polymorphisms (D, L, X) are linked to an increased risk of RA.
- The MBL B allele appears to have a protective effect against the development of pSS.
- These findings highlight the role of MBL genetics in the pathogenesis of autoimmune diseases.
