PMC:4521172 / 1908-6018 JSONTXT

{"project":"2_test","denotations":[{"id":"26284055-20852127-36586617","span":{"begin":523,"end":527},"obj":"20852127"},{"id":"26284055-22011404-36586618","span":{"begin":543,"end":547},"obj":"22011404"},{"id":"26284055-23152904-36586619","span":{"begin":549,"end":553},"obj":"23152904"},{"id":"26284055-22516608-36586620","span":{"begin":573,"end":577},"obj":"22516608"},{"id":"26284055-20852127-36586621","span":{"begin":748,"end":752},"obj":"20852127"},{"id":"26284055-25273270-36586622","span":{"begin":775,"end":779},"obj":"25273270"},{"id":"26284055-23953767-36586623","span":{"begin":795,"end":799},"obj":"23953767"},{"id":"26284055-16023210-36586624","span":{"begin":1024,"end":1028},"obj":"16023210"},{"id":"26284055-19609346-36586625","span":{"begin":1047,"end":1051},"obj":"19609346"},{"id":"26284055-19594626-36586626","span":{"begin":1384,"end":1388},"obj":"19594626"},{"id":"26284055-9806066-36586628","span":{"begin":1547,"end":1551},"obj":"9806066"},{"id":"26284055-16395391-36586629","span":{"begin":1750,"end":1754},"obj":"16395391"},{"id":"26284055-11528516-36586630","span":{"begin":1862,"end":1866},"obj":"11528516"},{"id":"26284055-20065005-36586631","span":{"begin":1888,"end":1892},"obj":"20065005"},{"id":"26284055-16738667-36586632","span":{"begin":1918,"end":1922},"obj":"16738667"},{"id":"26284055-24126531-36586633","span":{"begin":1936,"end":1940},"obj":"24126531"},{"id":"26284055-19086549-36586634","span":{"begin":1978,"end":1982},"obj":"19086549"},{"id":"26284055-17922403-36586635","span":{"begin":2020,"end":2024},"obj":"17922403"},{"id":"26284055-20650301-36586636","span":{"begin":2042,"end":2046},"obj":"20650301"},{"id":"26284055-22050925-36586637","span":{"begin":2078,"end":2082},"obj":"22050925"},{"id":"26284055-25312983-36586638","span":{"begin":2097,"end":2101},"obj":"25312983"},{"id":"26284055-22302853-36586639","span":{"begin":2137,"end":2141},"obj":"22302853"},{"id":"26284055-24035792-36586640","span":{"begin":2169,"end":2173},"obj":"24035792"},{"id":"26284055-23000377-36586641","span":{"begin":2220,"end":2224},"obj":"23000377"},{"id":"26284055-22002015-36586642","span":{"begin":2269,"end":2273},"obj":"22002015"},{"id":"26284055-16395391-36586643","span":{"begin":2711,"end":2715},"obj":"16395391"},{"id":"26284055-11393663-36586645","span":{"begin":3102,"end":3106},"obj":"11393663"},{"id":"26284055-23000377-36586646","span":{"begin":3122,"end":3126},"obj":"23000377"},{"id":"26284055-9806066-36586647","span":{"begin":3308,"end":3312},"obj":"9806066"},{"id":"26284055-12641410-36586648","span":{"begin":3490,"end":3494},"obj":"12641410"},{"id":"26284055-16738667-36586649","span":{"begin":3608,"end":3612},"obj":"16738667"},{"id":"26284055-24126531-36586650","span":{"begin":3801,"end":3805},"obj":"24126531"}],"text":"Introduction\nMalaria is a mosquito borne protozoan infection caused by Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. In a recent report, World Health Organization (WHO) estimates about198 million cases in 2013 and 1.2 billion subjects are at high riskworldwide (WHO, 2014). Majority of malarial death is a result of P. falciparum infection which leads to severe malaria characterized by cerebral malaria (CM), multi-organ dysfunction (MOD), and non-cerebral severe malaria (NCSM) (Buffet et al., 2011; Panda et al., 2011, 2012; Pattanaik et al., 2012). The pathogenesis of malaria is complex and the severity depends on parasite virulence, transmission dynamics, genetic factors, and host immune response (Buffet et al., 2011; Mangano and Modiano, 2014; White et al., 2014). Malaria infection elicits both innate and adaptive immune response of the host. The innate immune system is composed of diverse pattern-recognizing receptors or soluble pathogen-recognizing molecules (PRMs) (Thiel et al., 2006; Barreiro et al., 2009), which recognize specific molecular motifs on the surfaces of virus, bacteria and parasites. Mannose binding lectin is a liver derived soluble PRMs which play an important role in the innate immune response. MBL binds to sugars on the surface of pathogenic micro-organisms and triggers the complement activation system (Ip et al., 2009). MBL has been shown to bind to parasite infected erythrocytes (Garred et al., 2003b) and children deficient in MBL are prone to severe malaria (Luty et al., 1998), indicating an important role for MBL in protection against P. falciparum malaria.\nThe human MBL is a 32 KDa protein consisting of 248 amino acids encoded by MBL2 mapped to 10q21.1 (Garred et al., 2006). Common MBL2 genetic variants have been associated with various diseases such as filariasis (Choi et al., 2001; Meyrowitsch et al., 2010), malaria (Boldt et al., 2006; Jha et al., 2014), leishmaniasis (Asgharzadeh et al., 2007), leprosy (de Messias-Reason et al., 2007; Sapkota et al., 2010), tuberculosis (Singla et al., 2012; Chen et al., 2014), trypanosomiasis (Weitzel et al., 2012), HIV infection(Li et al., 2013), systemic lupus erythematosus (Panda et al., 2013), and rheumatoid arthritis (Martiny et al., 2012). The MBL2 gene consists of four exons. Although several single nucleotide polymorphisms (SNPs) have been reported, three SNPs in exon 1 (codons 52: rs5030737, C \u003e T, Arg\u003eCys; codon 54: rs1800450, G \u003e A, Gly\u003e Asp and codon 57: rs1800451, G \u003eA,Gly\u003eGlu) are of importance since they affect plasma levels of MBL. Variants are denoted as D (codon 52), B (codon 54), and C (codon 57), whereas A is the common wild type allele (Garred et al., 2006). In addition, two other functional polymorphisms at promoter region of the MBL2 gene have been reported (−550: rs11003125,G \u003e C, H/L and−221: rs7096206, C \u003e G, X/Y) which have been shown to affect plasma MBL levels (Garred et al., 2003a). Furthermore, some reports have shown an association of combined exon1 and promoter MBL2 polymorphisms with plasma levels of MBL (Tsutsumi et al., 2001; Panda et al., 2013).\nThe association between MBL2 polymorphism and P. falciparum malaria in Gabonese children has been reported in several studies but it has shown contradictory results. Luty et al. (1998), showed an association between codon 54 and 57 variants with susceptibility to severe malaria. On the contrary, another study failed to show similar association (Mombo et al., 2003). Interestingly, a novel mutation (−797C \u003e A) has been linked to susceptibility to severe malaria (Boldt et al., 2006).\nA recent study in Indian population revealed association between MBL2 LYPA haplotype with protection and MBL2 LXPA haplotype with increased susceptibility to severe malaria (Jha et al., 2014). To the best of our knowledge, there are no studies on the association of plasma MBL and common MBL2 polymorphism with P. falciparum malaria in well-defined clinical phenotypes. We report an association between low plasma MBL and MBL low producer genotypes with multi organ dysfunction in Odisha, India."}

{"project":"PubTator4TogoVar","denotations":[{"id":"25765","span":{"begin":2423,"end":2432},"obj":"SNP"},{"id":"25770","span":{"begin":2460,"end":2469},"obj":"SNP"},{"id":"25775","span":{"begin":2501,"end":2510},"obj":"SNP"},{"id":"25782","span":{"begin":2859,"end":2868},"obj":"SNP"}],"attributes":[{"id":"A25765","pred":"resolved_to","subj":"25765","obj":"tmVar:rs5030737;VariantGroup:3;CorrespondingGene:4153;RS#:5030737;CorrespondingSpecies:9606"},{"id":"A25770","pred":"resolved_to","subj":"25770","obj":"tmVar:rs1800450;VariantGroup:1;CorrespondingGene:4153;RS#:1800450;CorrespondingSpecies:9606"},{"id":"A25775","pred":"resolved_to","subj":"25775","obj":"tmVar:rs1800451;VariantGroup:0;CorrespondingGene:4153;RS#:1800451;CorrespondingSpecies:9606"},{"id":"A25782","pred":"resolved_to","subj":"25782","obj":"tmVar:rs7096206;VariantGroup:2;CorrespondingGene:4153;RS#:7096206;CorrespondingSpecies:9606"}],"text":"Introduction\nMalaria is a mosquito borne protozoan infection caused by Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. In a recent report, World Health Organization (WHO) estimates about198 million cases in 2013 and 1.2 billion subjects are at high riskworldwide (WHO, 2014). Majority of malarial death is a result of P. falciparum infection which leads to severe malaria characterized by cerebral malaria (CM), multi-organ dysfunction (MOD), and non-cerebral severe malaria (NCSM) (Buffet et al., 2011; Panda et al., 2011, 2012; Pattanaik et al., 2012). The pathogenesis of malaria is complex and the severity depends on parasite virulence, transmission dynamics, genetic factors, and host immune response (Buffet et al., 2011; Mangano and Modiano, 2014; White et al., 2014). Malaria infection elicits both innate and adaptive immune response of the host. The innate immune system is composed of diverse pattern-recognizing receptors or soluble pathogen-recognizing molecules (PRMs) (Thiel et al., 2006; Barreiro et al., 2009), which recognize specific molecular motifs on the surfaces of virus, bacteria and parasites. Mannose binding lectin is a liver derived soluble PRMs which play an important role in the innate immune response. MBL binds to sugars on the surface of pathogenic micro-organisms and triggers the complement activation system (Ip et al., 2009). MBL has been shown to bind to parasite infected erythrocytes (Garred et al., 2003b) and children deficient in MBL are prone to severe malaria (Luty et al., 1998), indicating an important role for MBL in protection against P. falciparum malaria.\nThe human MBL is a 32 KDa protein consisting of 248 amino acids encoded by MBL2 mapped to 10q21.1 (Garred et al., 2006). Common MBL2 genetic variants have been associated with various diseases such as filariasis (Choi et al., 2001; Meyrowitsch et al., 2010), malaria (Boldt et al., 2006; Jha et al., 2014), leishmaniasis (Asgharzadeh et al., 2007), leprosy (de Messias-Reason et al., 2007; Sapkota et al., 2010), tuberculosis (Singla et al., 2012; Chen et al., 2014), trypanosomiasis (Weitzel et al., 2012), HIV infection(Li et al., 2013), systemic lupus erythematosus (Panda et al., 2013), and rheumatoid arthritis (Martiny et al., 2012). The MBL2 gene consists of four exons. Although several single nucleotide polymorphisms (SNPs) have been reported, three SNPs in exon 1 (codons 52: rs5030737, C \u003e T, Arg\u003eCys; codon 54: rs1800450, G \u003e A, Gly\u003e Asp and codon 57: rs1800451, G \u003eA,Gly\u003eGlu) are of importance since they affect plasma levels of MBL. Variants are denoted as D (codon 52), B (codon 54), and C (codon 57), whereas A is the common wild type allele (Garred et al., 2006). In addition, two other functional polymorphisms at promoter region of the MBL2 gene have been reported (−550: rs11003125,G \u003e C, H/L and−221: rs7096206, C \u003e G, X/Y) which have been shown to affect plasma MBL levels (Garred et al., 2003a). Furthermore, some reports have shown an association of combined exon1 and promoter MBL2 polymorphisms with plasma levels of MBL (Tsutsumi et al., 2001; Panda et al., 2013).\nThe association between MBL2 polymorphism and P. falciparum malaria in Gabonese children has been reported in several studies but it has shown contradictory results. Luty et al. (1998), showed an association between codon 54 and 57 variants with susceptibility to severe malaria. On the contrary, another study failed to show similar association (Mombo et al., 2003). Interestingly, a novel mutation (−797C \u003e A) has been linked to susceptibility to severe malaria (Boldt et al., 2006).\nA recent study in Indian population revealed association between MBL2 LYPA haplotype with protection and MBL2 LXPA haplotype with increased susceptibility to severe malaria (Jha et al., 2014). To the best of our knowledge, there are no studies on the association of plasma MBL and common MBL2 polymorphism with P. falciparum malaria in well-defined clinical phenotypes. We report an association between low plasma MBL and MBL low producer genotypes with multi organ dysfunction in Odisha, India."}

{"project":"PubTatorOnTogoVar","denotations":[{"id":"25765","span":{"begin":2423,"end":2432},"obj":"SNP"},{"id":"25770","span":{"begin":2460,"end":2469},"obj":"SNP"},{"id":"25775","span":{"begin":2501,"end":2510},"obj":"SNP"},{"id":"25782","span":{"begin":2859,"end":2868},"obj":"SNP"},{"id":"T1","span":{"begin":2423,"end":2432},"obj":"SNP"},{"id":"T2","span":{"begin":2460,"end":2469},"obj":"SNP"},{"id":"T3","span":{"begin":2501,"end":2510},"obj":"SNP"},{"id":"T4","span":{"begin":2859,"end":2868},"obj":"SNP"}],"attributes":[{"id":"A25765","pred":"resolved_to","subj":"25765","obj":"tmVar:rs5030737;VariantGroup:3;CorrespondingGene:4153;RS#:5030737;CorrespondingSpecies:9606"},{"id":"A25770","pred":"resolved_to","subj":"25770","obj":"tmVar:rs1800450;VariantGroup:1;CorrespondingGene:4153;RS#:1800450;CorrespondingSpecies:9606"},{"id":"A25775","pred":"resolved_to","subj":"25775","obj":"tmVar:rs1800451;VariantGroup:0;CorrespondingGene:4153;RS#:1800451;CorrespondingSpecies:9606"},{"id":"A25782","pred":"resolved_to","subj":"25782","obj":"tmVar:rs7096206;VariantGroup:2;CorrespondingGene:4153;RS#:7096206;CorrespondingSpecies:9606"},{"id":"A1","pred":"resolved_to","subj":"T1","obj":"tmVar:rs5030737;VariantGroup:3;CorrespondingGene:4153;RS#:5030737;CorrespondingSpecies:9606"},{"id":"A2","pred":"resolved_to","subj":"T2","obj":"tmVar:rs1800450;VariantGroup:1;CorrespondingGene:4153;RS#:1800450;CorrespondingSpecies:9606"},{"id":"A3","pred":"resolved_to","subj":"T3","obj":"tmVar:rs1800451;VariantGroup:0;CorrespondingGene:4153;RS#:1800451;CorrespondingSpecies:9606"},{"id":"A4","pred":"resolved_to","subj":"T4","obj":"tmVar:rs7096206;VariantGroup:2;CorrespondingGene:4153;RS#:7096206;CorrespondingSpecies:9606"}],"text":"Introduction\nMalaria is a mosquito borne protozoan infection caused by Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. In a recent report, World Health Organization (WHO) estimates about198 million cases in 2013 and 1.2 billion subjects are at high riskworldwide (WHO, 2014). Majority of malarial death is a result of P. falciparum infection which leads to severe malaria characterized by cerebral malaria (CM), multi-organ dysfunction (MOD), and non-cerebral severe malaria (NCSM) (Buffet et al., 2011; Panda et al., 2011, 2012; Pattanaik et al., 2012). The pathogenesis of malaria is complex and the severity depends on parasite virulence, transmission dynamics, genetic factors, and host immune response (Buffet et al., 2011; Mangano and Modiano, 2014; White et al., 2014). Malaria infection elicits both innate and adaptive immune response of the host. The innate immune system is composed of diverse pattern-recognizing receptors or soluble pathogen-recognizing molecules (PRMs) (Thiel et al., 2006; Barreiro et al., 2009), which recognize specific molecular motifs on the surfaces of virus, bacteria and parasites. Mannose binding lectin is a liver derived soluble PRMs which play an important role in the innate immune response. MBL binds to sugars on the surface of pathogenic micro-organisms and triggers the complement activation system (Ip et al., 2009). MBL has been shown to bind to parasite infected erythrocytes (Garred et al., 2003b) and children deficient in MBL are prone to severe malaria (Luty et al., 1998), indicating an important role for MBL in protection against P. falciparum malaria.\nThe human MBL is a 32 KDa protein consisting of 248 amino acids encoded by MBL2 mapped to 10q21.1 (Garred et al., 2006). Common MBL2 genetic variants have been associated with various diseases such as filariasis (Choi et al., 2001; Meyrowitsch et al., 2010), malaria (Boldt et al., 2006; Jha et al., 2014), leishmaniasis (Asgharzadeh et al., 2007), leprosy (de Messias-Reason et al., 2007; Sapkota et al., 2010), tuberculosis (Singla et al., 2012; Chen et al., 2014), trypanosomiasis (Weitzel et al., 2012), HIV infection(Li et al., 2013), systemic lupus erythematosus (Panda et al., 2013), and rheumatoid arthritis (Martiny et al., 2012). The MBL2 gene consists of four exons. Although several single nucleotide polymorphisms (SNPs) have been reported, three SNPs in exon 1 (codons 52: rs5030737, C \u003e T, Arg\u003eCys; codon 54: rs1800450, G \u003e A, Gly\u003e Asp and codon 57: rs1800451, G \u003eA,Gly\u003eGlu) are of importance since they affect plasma levels of MBL. Variants are denoted as D (codon 52), B (codon 54), and C (codon 57), whereas A is the common wild type allele (Garred et al., 2006). In addition, two other functional polymorphisms at promoter region of the MBL2 gene have been reported (−550: rs11003125,G \u003e C, H/L and−221: rs7096206, C \u003e G, X/Y) which have been shown to affect plasma MBL levels (Garred et al., 2003a). Furthermore, some reports have shown an association of combined exon1 and promoter MBL2 polymorphisms with plasma levels of MBL (Tsutsumi et al., 2001; Panda et al., 2013).\nThe association between MBL2 polymorphism and P. falciparum malaria in Gabonese children has been reported in several studies but it has shown contradictory results. Luty et al. (1998), showed an association between codon 54 and 57 variants with susceptibility to severe malaria. On the contrary, another study failed to show similar association (Mombo et al., 2003). Interestingly, a novel mutation (−797C \u003e A) has been linked to susceptibility to severe malaria (Boldt et al., 2006).\nA recent study in Indian population revealed association between MBL2 LYPA haplotype with protection and MBL2 LXPA haplotype with increased susceptibility to severe malaria (Jha et al., 2014). To the best of our knowledge, there are no studies on the association of plasma MBL and common MBL2 polymorphism with P. falciparum malaria in well-defined clinical phenotypes. We report an association between low plasma MBL and MBL low producer genotypes with multi organ dysfunction in Odisha, India."}