The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a...

Mannose-binding lectin (MBL) enhances opsonization and activates complement. Dysfunctional alleles of MBL have been associated with low plasma concentrations of MBL and increased risk of systemic lupus erythematosus (SLE), but genotyping studies have shown inconsistent results. We performed case-control studies of the MBL polymorphisms in 2 Caucasian cohorts and a meta-analysis incorporating all published results of MBL genotyping in SLE to explore whether the MBL functional variants are associated with SLE.

MBL genotypes at 7 single-nucleotide polymorphisms were sequenced in 96 European American patients with SLE and 96 age-, race-, and sex-matched controls. MBL codons 52, 54, and 57 were genotyped in 285 German patients with SLE and 200 race-matched controls. Allele frequencies of all known variants were tallied for meta-analysis.

Although there was a trend toward association with MBL polymorphisms in both patient cohorts evaluated, none of them was significantly associated with SLE on its own. Seventeen comparisons from 15 studies were included in the meta-analysis. Publication bias was excluded by Egger's regression test (P = 0.14). The overall odds ratio for MBL codon 54 variant B was 1.406 (95% confidence interval 1.221-1.608; P < 0.001). Stratification by ethnicity showed significantly increased odds ratios for association of the MBL codon 54 B variant with SLE in African, Asian, and Caucasian cohorts.

Meta-analysis of all available studies on MBL polymorphisms and SLE shows that MBL variant alleles such as MBL exon 1 codon 54 B, promoter -550 L, and promoter -221 X are SLE risk factors. This association is robust and persists after incorporation of data from our 2 cohorts in which the association failed to reach significance.