Mannose‐binding lectin and MBL‐associated serine protease‐2 gene polymorphisms in a Brazilian population from Rio de Janeiro

Abstract

Mannose-binding lectin (MBL) is a protein able to bind to carbohydrate patterns on pathogen membranes; upon MBL binding, its' associated serine protease MBL-associated serine protease type 2 (MASP2) is autoactivated, promoting the activation of complement via the lectin pathway. For both MBL2 and MASP2 genes, the frequencies of polymorphisms are extremely variable between different ethnicities, and this aspect has to be carefully considered when performing genetic studies. While polymorphisms in the MBL-encoding gene (MBL2) have been associated, depending upon ethnicity, with several diseases in different populations, little is known about the distribution of MASP2 gene polymorphisms in human populations. The aim of our study was thus to determine the frequencies of MBL2 (exon 1 and promoter) and MASP2 (p.D371Y) polymorphisms in a Brazilian population from Rio de Janeiro. A total of 294 blood donor samples were genotyped for 27 polymorphisms in the MBL2 gene by direct sequencing of a region spanning from the promoter polymorphism H/L rs11003125 to the rs1800451 polymorphism (at codon 57 in the first exon of the gene). Genotyping for MASP2 p.D371Y was carried out using fluorogenic probes. To our knowledge, this is the first study reporting the prevalence of the MASP2 p.D371Y polymorphism in a Brazilian population. The C allele frequency 39% is something intermediate between the reported 14% in Europeans and 90% in Sub-Saharan Africans. MBL2 polymorphisms frequencies were quite comparable to those previously reported for admixed Brazilians. Both MBL2 and MASP2 polymorphisms frequencies reported in our study for the admixed Brazilian population are somehow intermediate between those reported in Europeans and Africans, reflecting the ethnic composition of the southern Brazilian population, estimated to derive from an admixture of Caucasian (31%), African (34%) and Native American (33%) populations. In conclusion, our population genetic study describes the frequencies of MBL2 and MASP2 functional SNPs in a population from Rio de Janeiro, with the aim of adding new information concerning the distribution of these SNPs in a previously unanalysed Brazilian population, thus providing a new genetic tool for the evaluation of the association of MBL2 and MASP2 functional SNPs with diseases in Brazil, with particular emphasis on the state of Rio de Janeiro.

Mannose-binding lectin 2 (MBL2) gene polymorphisms do not influence frequency of infections in chronic lymphocytic leukemia patients

“…Although MBL2 gene polymorphisms were not evaluated in healthy subjects, the present data showed similar allele and genotype frequencies in CLL patients as healthy donors from other studies 26., 27.. Regarding MBL2 gene polymorphisms in respect to occurrence of infections, it was not possible to demonstrate a significant association between polymorphisms of the - 221 and - 550 promoter regions and exon 1 of the MBL2 gene with higher risk of infection in CLL patients.…”

The Clinical Value of Ficolin-3 Gene Polymorphism in Rheumatic Heart Disease. An Egyptian Adolescents Study

“…Signi cant differences in the distribution of MBL2 and FCN3 alleles and genotypes have been identi ed among the population from various continents. These distinctive genetic patterns may almost certainly affect serum MBL and colin-3 levels, accordingly modifying worldwide susceptibility for the disease [60,61]. What's more, the presence of the C allele in controls in highly signi cant patterns as compared to RF patients could show that the presence of the C allele may have a defensive action against the occurrence of RF and RHD.…”

Association of ficolin-2 (FCN2) functional polymorphisms and protein levels with rheumatic fever and rheumatic heart disease: relationship with cardiac function

“…Many studies have revealed significantly different distribution of MBL2 and FCN2 alleles, genotypes and haplotypes among populations from different continents. These different genetic patterns may likely contribute to altered serum ficolin-2 and MBL levels, thus modulating disease susceptibility among world populations [35, 36].…”