Mannose-binding lectin (MBL) codon 54 gene polymorphism protects against development of pre-eclampsia, HELLP syndrome and pre-eclampsia-associated intrauterine growth restriction

Abstract

Insufficient invasion of the spiral arteries by trophoblast cells is associated with the etiology of pre-eclampsia, the syndrome of hemolysis, elevated liver enzymes and low platelet counts (HELLP) and pre-eclampsia-associated intrauterine growth restriction (IUGR). Mannose-binding lectin (MBL) is a component of the innate immune system. MBL-mediated activation of the complement cascade is an important event in the destruction of invading trophoblasts. The gene coding for MBL is polymorphic, and variant alleles result in greatly reduced circulating MBL levels. The aim of this study was to test the association between an MBL polymorphism and pre-eclampsia, HELLP syndrome and IUGR. DNA was extracted from buccal swabs of 51 women with pre-eclampsia, 81 women with HELLP syndrome and 184 healthy pregnant controls. Aliquots were tested for a single nucleotide MBL gene polymorphism at codon 54 by PCR and endonuclease digestion. Homozygosity for the wild-type allele was more frequent in patients with pre-eclampsia (P = 0.04) and HELLP syndrome (P = 0.02) when compared with controls. The presence of the variant allele was more prevalent among controls than in women with pre-eclampsia (P = 0.02) or HELLP syndrome (P = 0.028). Twenty-two (55%) patients with pre-eclampsia and 43 (53%) women with HELLP syndrome delivered an IUGR neonate. MBL-54 heterozygosity was more frequent in controls (27.2%) than in pre-eclamptic women (4.5%, P = 0.025) and those with HELLP syndrome (11.7%, P = 0.05) who delivered an IUGR neonate. Genotype frequencies of neonates born to mothers in all study groups were similar. Carriage of the MBL codon 54 polymorphism protects against pre-eclampsia, HELLP syndrome and IUGR and implies that an MBL-mediated event might be involved in the pathogenesis of these disorders.

Mannose-binding lectin genotypes and pre-eclampsia: A case-control study

“…In contrast to our data Sziller et al [32] published data demonstrating that the MBL codon 54 gene polymorphism, compatible with low MBL production, protects against the development of pre-eclampsia. Differences can be explained by differences in study design.…”

Genetic Variation in Chlamydia Trachomatis and Their Hosts: Impact on Disease Severity and Tissue Tropism

“…In other studies of genital tract infections with C. trachomatis in women, no association was found between TFI and polymorphisms in TLR4 and its coreceptor CD14, IL-1β and IL-1RN [121,122]. However, women diagnosed with TFI were found to express the variant allele B of mannose-binding lectin-2, while the wildtype allele A was associated with an absence of disease complications [29]. …”

“…This is certainly true for both prokaryotic and eukaryotic pathogens, and their capability for DNA exchange is central to virulence gene and fitness trait acquisition [21,22]. While host genetics may contribute to disease severity [12-17,23-29] the pathogen must also successfully evolve to survive in the hostile host environment (Figure 2), and C. trachomatis has developed a number of ways to adapt within host intracellular niches. Prokaryotes acquire beneficial new genetic traits via several standard mechanisms.…”

Genetic Aspects of Preeclampsia and the HELLP Syndrome

“…MBL is present in the spiral arteries, particularly in those containing endovascular trophoblasts. MBL-mediated activation of the complement cascade is an important event in destruction of invading EVTs [67]. …”