Mannose-Binding Lectin Codon 54 Gene Polymorphism and Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis

Abstract

Mannose-binding lectin (MBL) plays a key role in the human innate immune response. It has been shown that polymorphisms in the MBL2 gene, particularly at codon 54 (variant allele B; wild-type allele designated as A), impact upon host susceptibility to Candida infection. This systematic review and meta-analysis were performed to assess the association between MBL2 codon 54 genotype and vulvovaginal candidiasis (VVC) or recurrent VVC (RVVC). Studies were searched in MEDLINE, SCOPUS, and ISI Web of Science until April 2013. Five studies including 704 women (386 cases and 318 controls) were part of the meta-analysis, and pooled ORs were calculated using the random effects model. For subjects with RVVC, ORs of AB versus AA and of BB versus AA were 4.84 (95% CI 2.10–11.15; P for heterogeneity = 0.013; I 2 = 68.6%) and 12.68 (95% CI 3.74–42.92; P for heterogeneity = 0.932, I 2 = 0.0%), respectively. For subjects with VVC, OR of AB versus AA was 2.57 (95% CI 1.29–5.12; P for heterogeneity = 0.897; I 2 = 0.0%). This analysis indicates that heterozygosity for the MBL2 allele B increases significantly the risk for both diseases, suggesting that MBL may influence the women's innate immunity in response to Candida.

Mutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM)

“…Polymorphisms in the MBL2 gene are more frequent in African-Americans and multiple studies have suggested an association between MBL2 genetic variants that result in diminished MBL2 protein levels and preterm birth, and conditions commonly found in preterm pregnancies including chorioamnionitis (Annells et al 2004(Annells et al , 2005Gibson et al 2011;Jaffe et al 2013;Capece et al 2014;Nedovic et al 2014). Our discovery of a nonsense mutations that significantly truncates the MBL2 protein is thus consistent with the notion that loss of this antimicrobial protein increases risk of prematurity.…”

“…; Nedovic et al. ). Our discovery of a nonsense mutations that significantly truncates the MBL2 protein is thus consistent with the notion that loss of this antimicrobial protein increases risk of prematurity.…”

Fungal interactions with the human host: exploring the spectrum of symbiosis

“…This study also found higher frequencies of a mutation causing a premature stop codon in the C-type lectin receptor Dectin-1 in women with RVVC, which mediates IL-22 production [48]. Polymorphisms in mannose binding lectin (MBL), a component of innate immunity that triggers complement activation, are also found at higher frequencies in RVVC patients and are associated with leading reduced vaginal MBL levels [49,50]. Overall, these studies support the concept that pathways important in mucosal tolerance that may limit innate responsiveness to a commensal symbiont promote resistance to RVVC.…”

Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland

“…This is in contrast to vulvovaginal candidiasis, where a recent meta-analysis demonstrated an increased risk in women harboring the MBL2 exon 1 codon 54 (A/B) variant (36). We can only speculate that other PRR (e.g.…”