Association of mannose-binding lectin gene (MBL2) polymorphisms with rheumatoid arthritis in an Indian cohort of case-control samples

Abstract

Single nucleotide polymorphisms in the mannose-binding lectin (MBL2) gene, as well as the serum MBL2 level, have been associated with various autoimmune diseases. We investigated whether such polymorphisms and/or the serum MBL2 level were associated with rheumatoid arthritis (RA) in an Indian population. The frequency of the B variant (codon 54) of the MBL2 gene was quite frequent in the healthy Indian population and was significantly (P=6.35·10 À6 ) lower in RA patients. We replicated this association (P=1.78·10 À5 ) in an independent cohort of control individuals. Promoter polymorphism at À550 nt showed a significant overrepresentation (P=0.003) of the minor allele G in severe RA patients compared with the less severe group. Haplotype LYA frequency was significantly (P=0.03) high in the less severe group, while the frequency of the HYA haplotype was significantly (P=0.04) increased in the severe RA patients. No statistically significant difference in serum MBL2 was observed as a whole, but the individuals homozygous for the LYA haplotype had significantly lower (P=0.017) serum MBL2 levels compared with individuals homozygous for the HYA haplotype. Therefore, the B variant of the MBL2 gene may be associated with protection from RA in our study population, and the promoter polymorphism (À550 nt) seems to have some role in disease progression.

Association of MIF−173G/C and MBL2 codon 54 gene polymorphisms with rheumatoid arthritis: A meta-analysis

“…However, Palomino-Morales et al found no association of this polymorphism and RA patients from northwestern Spain [29]. With respect to the association of MBL2 codon 54 polymorphism and RA, results are inconsistent across studies as well [20,21]. This discrepancy may be attributed to small sample sized association studies lack statistical power, racial and ethnic differences, publication bias or uncorrected multiple hypothesis testing.…”

“…MBL is thought to be implicated in the innate immunity of host defense that works prior to the establishment of adaptive immune system [20]. Some autoantibody are produced in conjunction with manifestations of RA, and rheumatoid factors (RFs) are the characteristic autoantibodies, binding to the Fc region of agalactosylated IgG (IgG 0 ) molecules [21,22]. RFs were found increased in the sera of RA patients [23].…”

“…The MBL gene is located on the long arm of chromosome 10 at 10q11.2-q21 and contains 4 exons [25] (Fig. 1, [21]). Exon 1 codes for the cysteine-rich region and a part of the collagenous domain [26].…”

The MBL2 ‘LYQA Secretor’ Haplotype Is an Independent Predictor of Postoperative Myocardial Infarction in Whites Undergoing Coronary Artery Bypass Graft Surgery

“…For example, decreased MBL serum levels have been shown to be associated with an increased risk of infection in children and immunocompromised individuals, including recurrent respiratory infections, meningococcal disease, and Pseudomonas aeruginosa infection in burn patients. 30 Alternatively, MBL recognition of self-antigens has been demonstrated in several sterile inflammatory processes, including thoracoabdominal aortic aneurysms, 8 IgA nephritis, 31 rheumatoid arthritis, 32 atherosclerosis, 10 diabetes, 7,12 cancer, 33 and coronary artery disease. 6,14 Moreover, inhibition of MBL was recently shown to reduce infarct size in an experimental model of myocardial infarction.…”

Λεκτίνη συνδεόμενη με τη μαννόζη (mannose-binding lectin, MBL) και περιγεννητικές λοιμώξεις

“…Δεδομένα ενισχύουν την άποψη ότι η MBL ανεπάρκεια σχετίζεται με τις κλινικές εκδηλώσεις και τη σταδιοποίηση της ΡΑ [62,173,174,175]. Σε μελέτη επί 99 ασθενών που παρουσίαζαν τη συγκεκριμένη αυτοάνοση νόσο, δεν παρατηρήθηκε σημαντική διαφορά ως προς τη συγκέντρωση της πρωτεΐνης MBL μεταξύ ασθενών και φυσιολογικών ατόμων [176].…”