Extreme high prevalence of a defective mannose-binding lectin (MBL2) genotype in native South American West Andean populations.

José Raul Sandoval,Peter Garred,Margarita Velazquez-Reinoso,Gianfranco De Stefano,Cesar Ñique,Hans O Madsen,Ricardo Fujita,Jaime Descailleaux-Dulanto,Robert B Sim

doi:10.1371/journal.pone.0108943

Abstract

Mannose-binding lectin (MBL) is one of the five recognition molecules in the lectin complement pathway. Common variant alleles in the promoter and structural regions of the human MBL gene (MBL2) influence the stability and serum concentration of the protein. Epidemiological studies have shown that MBL2 variant alleles are associated with susceptibility to and the course of different types of infectious and inflammatory conditions. However, it has been suggested that these alleles are maintained in different populations due to selected advantages for carriers. We investigated the MBL2 allelic variation in indigenous individuals from 12 different West Central South America localities spanning from the desert coast, high altitude Andean plates and the Amazon tropical forest within the territories of Peru (n = 249) (Departments of Loreto, Ucayali, Lambayeque, Junin, Ayacucho, Huancayo and Puno), and Ecuador (n = 182) (Region of Esmeraldas and Santo Domingo de los Colorados). The distribution of MBL2 genotypes among the populations showed that the defective variant LYPB haplotype was very common. It showed the highest frequencies in Puno (Taquile (0.80), Amantani (0.80) and Anapia (0.58) islander communities of the Lake Titicaca), but lower frequencies of 0.22 in Junin (Central Andean highland) and Ucayali (Central Amazonian forest), as well as 0.27 and 0.24 in the Congoma and Cayapa/Chachis populations in the Amazonian forest in Ecuador were also observed. Our results suggest that the high prevalence of the MBL2 LYPB variant causing low levels of functional MBL in serum may mainly reflect a random distribution due to a population bottleneck in the founder populations.

Highlights

Mannose-binding lectin (MBL) is a pattern recognition molecule that recognizes sugars such as terminal mannose and N-acetylglucosamine groups common on the surface of various microorganisms [1]
To get insight to the distribution of the MBL2 alleles and haplotypes in different indigenous people of South America we have investigated populations situated in different regions at the Pacific desert coast, high altitude Andean plates and the Amazonian forest within the territories of the Countries of Peru and Ecuador
Examination of MBL2 haplotypes revealed that the LYPB was common in all of the studied populations, but that the variants LYQC and HYPD were virtually absent (Table 1)

Summary

Introduction

Mannose-binding lectin (MBL) is a pattern recognition molecule that recognizes sugars such as terminal mannose and N-acetylglucosamine groups common on the surface of various microorganisms [1]. MBL plays a role in innate immune defence by mediating activation of the lectin complement pathway via three associated serine proteases (MASP-1, MASP-2 and MASP-3, respectively) and by enhancing phagocytosis of microorganisms and dying host cells [2]. It shares features with other recognition molecules in the lectin complement pathway, ficolin-1, ficolin-2 and ficolin-3 [3] and collectin-11 [4]. Exon 1 encodes the signal peptide, a cysteine rich domain and seven copies of a repeated Glycine-Xaa-Yaa motif typical for the triple helix formation of collagen structures (Xaa and Yaa indicate any amino acid) This pattern is continued by additional 12 Glycine-Xaa-Yaa repeats in exon 2. When isolated from serum the protein consists of 3 to 6 identical oligomers

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Conclusion