title: MBL2 variations and malaria susceptibility in Indian populations.
abstract: Human mannose-binding lectin (MBL) encoded by the MBL2 gene is a pattern recognition protein and has been associated with many infectious diseases, including malaria. We sought to investigate the contribution of functional MBL2 gene variations to Plasmodium falciparum malaria in well-defined cases and in matched controls. We resequenced the 8.7 kb of the entire MBL2 gene in 434 individuals clinically classified with malaria from regions of India where malaria is endemic. The study cohort included 176 patients with severe malaria, 101 patients with mild malaria, and 157 ethnically matched asymptomatic individuals. In addition, 830 individuals from 32 socially, linguistically, and geographically diverse endogamous populations of India were investigated for the distribution of functional MBL2 variants. The MBL2 -221C (X) allelic variant is associated with increased risk of malaria (mild malaria odds ratio [OR] = 1.9, corrected P value [P(Corr)] = 0.0036; severe malaria OR = 1.6, P(Corr) = 0.02). The exon1 variants MBL2*B (severe malaria OR = 2.1, P(Corr) = 0.036; mild versus severe malaria OR = 2.5, P(Corr) = 0.039) and MBL2*C (mild versus severe malaria OR = 5.4, P(Corr) = 0.045) increased the odds of having malaria. The exon1 MBL2*D/*B/*C variant increased the risk for severe malaria (OR = 3.4, P(Corr) = 0.000045). The frequencies of low MBL haplotypes were significantly higher in severe malaria (14.2%) compared to mild malaria (7.9%) and asymptomatic (3.8%). The MBL2*LYPA haplotypes confer protection, whereas MBL2*LXPA increases the malaria risk. Our findings in Indian populations demonstrate that MBL2 functional variants are strongly associated with malaria and infection severity.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Aditya Nath
authors.initials: AN
authors.lastname: Jha
authors.forename: Pandarisamy
authors.initials: P
authors.lastname: Sundaravadivel
authors.forename: Vipin Kumar
authors.initials: VK
authors.lastname: Singh
authors.forename: Sudhanshu S
authors.initials: SS
authors.lastname: Pati
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Patra
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Thirumalaisamy P
authors.initials: TP
authors.lastname: Velavan
authors.forename: Lalji
authors.initials: L
authors.lastname: Singh
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D016778:Malaria, Falciparum / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010963:Plasmodium falciparum; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin