Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study

García-Laorden, M Isabel; Castro, Felipè Rodríguez de; Solé‐Violán, Jordi; Rajas, Olga; Blanquer, José; Borderías, Luis; Aspa, Javier; Briones, M. Luisa; Saavedra, Pedro; Marcos-Ramos, José Alberto; González-Quevedo, Nereida; Sologuren, Ithaisa; Herrera-Ramos, Estefanía; Ferrer, José M.; Rello, Jordi; Rodríguez-Gallego, Carlos

doi:10.1186/cc10030

Cited by 45 publications

(50 citation statements)

References 57 publications

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“…S1) [17]. As expected, pairwise LD (D') confirmed the existence of a very strong LD within MBL2 SNPs.…”

Section: Ld Of Mbl2 Sftpa1 Sftpa2 and Sftpd Genessupporting

confidence: 56%

“…Due to the existence of LD, only 177 of the 2,048 expected haplotypes encompassing SFTPD, SFTPA1, SFTPA2 and MBL2 were observed, and only 18 had frequencies higher than 1% (data not shown). We previously reported a protective effect of the 6A -1A 0 haplotypes on susceptibility to CAP [17]. When susceptibility to P-CAP was studied in the present study, the protective effect of these haplotypes was even higher when they co-segregate with the MBL2 XA variant (table 6).…”

Section: Susceptibility To P-cap Related To Haplotypes Encompassing Smentioning

confidence: 66%

“…We have previously genotyped polymorphisms in SFTPA1 (aa19 T/C, rs1059047; aa50 G/C, rs1136450; aa219 C/T, 4253527), SFTPA2 (aa9 A/C, rs1059046; aa91 G/C, rs17886395; aa223 C/A, rs4253527) and SFTPD (aa11 T/C, rs721917) genes in part of both patient and control groups [17]. Haplotypes were named as 6A n for SFTPA1 and 1A n for SFTPA2 based on previous nomenclature [21].…”

Section: Genotypingmentioning

confidence: 99%

“…Genomic DNA was isolated as previously described [17]. The following MBL2 polymorphisms were analysed as described elsewhere [20]: codon 52 C/T (rs5030737, allele D), codon 54 A/G (rs1800450, allele B), codon 57 A/G (rs1800451, allele C) and codon -221 G/C (rs7096206, alleles X/Y).…”

Section: Genotypingmentioning

confidence: 99%

“…SPs, but not MBL, take part in the first-line host defence in healthy lung. Genetic variability at genes coding for these SPs was associated with higher susceptibility and poor outcome of CAP [17]. The human SP-A locus consists of two similar genes, SFTPA1 and SFTPA2, localised within a cluster (10q21-24) that includes the SP-D gene (SFTPD) [15].…”

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confidence: 99%

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The role of mannose-binding lectin in pneumococcal infection

García‐Laorden¹,

Castro²,

Solé‐Violán³

et al. 2012

European Respiratory Journal

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The role of mannose-binding lectin (MBL) deficiency (MBL2; XA/O and O/O genotypes) in host defences remains controversial. The surfactant proteins (SP)-A1, -A2 and -D, other collectins whose genes are located near MBL2, are part of the first-line lung defence against infection. We analysed the role of MBL on susceptibility to pneumococcal infection and the existence of linkage disequilibrium (LD) among the four genes.We studied 348 patients with pneumococcal community-acquired pneumonia (P-CAP) and 2,110 controls. A meta-analysis of MBL2 genotypes in susceptibility to P-CAP and to invasive pneumococcal disease (IPD) was also performed. The extent of LD of MBL2 with SFTPA1, SFTPA2 and SFTPD was analysed.MBL2 genotypes did not associate with either P-CAP or bacteraemic P-CAP in the case-control study. The MBL-deficient O/O genotype was significantly associated with higher risk of IPD in a meta-analysis, whereas the other MBL-deficient genotype (XA/O) showed a trend towards a protective role. We showed the existence of LD between MBL2 and SP genes.The data do not support a role of MBL deficiency on susceptibility to P-CAP or to IPD. LD among MBL2 and SP genes must be considered in studies on the role of MBL in infectious diseases.

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“…S1) [17]. As expected, pairwise LD (D') confirmed the existence of a very strong LD within MBL2 SNPs.…”

Section: Ld Of Mbl2 Sftpa1 Sftpa2 and Sftpd Genessupporting

confidence: 56%

Section: Susceptibility To P-cap Related To Haplotypes Encompassing Smentioning

confidence: 66%

Section: Genotypingmentioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

mentioning

confidence: 99%

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The role of mannose-binding lectin in pneumococcal infection

García‐Laorden¹,

Castro²,

Solé‐Violán³

et al. 2012

European Respiratory Journal

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Collectins

Thiel¹,

Takahashi²

2013

Encyclopedia of Life Sciences

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Collectins are pattern‐recognition molecules of innate immunity and are involved in recognising pathogens and abnormal cells in an antibody‐independent manner. The name collectin is derived from the basic structure, consisting of a collagen‐like domain and a carbohydrate‐recognition domain (CRD), akin to lectins, which recognise sugars. The CRDs bind pathogen‐associated molecular patterns, which are chemical motifs exposed on the surface of pathogens and abnormal cells. Collectins are synthesised in many organs and some are circulating in blood, whereas others are localised to a tissue. Collectin genes are germinally present and therefore, their proteins are expressed at healthy state, affording an instant action. There are also a homologous protein family called ficolins, which are similar to collectins structurally and functionally. Mechanisms of actions include a direct opsonin activity, activation of complement pathways and coagulation, modulation of inflammation and adaptive immunity. Key Concepts: Collectins are molecules of innate immunity, which is the first line of host defence and is fully functional throughout the body and the life regardless of health. Collectins are pattern‐recognition molecules, which are able to identify invading pathogens and abnormal cells and tissues. Selected genetic mutations affect functions of collectins and are associated with reduced host defence mechanisms and developmental disorder. Some collectins are disease modifier, as deficiency itself may cause no problem whereas it may have adverse effect depending on type of disease, infection or sterile injury. Collectins have homology to ficolins structurally and functionally, and may share and substitute functions in host defence.

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