MBL genotype and risk of invasive pneumococcal disease:: a case-control study

被引:232
作者
Roy, S
Knox, K
Segal, S
Griffiths, D
Moore, CE
Welsh, KI
Smarason, A
Day, NP
McPheat, WL
Crook, DW
Hill, AVS
机构
[1] John Radcliffe Hosp, Dept Microbiol, Oxford OX3 9DU, England
[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
[3] John Radcliffe Hosp, Dept Paediat, Oxford Vaccine Grp, Oxford OX3 9DU, England
[4] John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England
[5] Churchill Hosp, Dept Surg, Oxford OX3 7LJ, England
[6] AstraZeneca, Macclesfield, Cheshire, England
基金
英国惠康基金;
关键词
D O I
10.1016/S0140-6736(02)08516-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Streptococcus pneumoniae is a major cause of morbidity and mortality in developed and developing countries. No common genetic determinants of susceptibility have been defined. Mannose-binding lectin (MBL) is a key mediator of innate host immunity that activates the complement pathway and directly opsonises some infectious pathogens. Mutations in three codons in the MBL gene have been identified, and individuals homozygous for a mutant genotype have very little or no serum MBL. We did a case-control study in the UK to assess whether these mutant genotypes were associated with invasive pneumococcal disease. Methods The frequencies of genotypes defined by the three mutations in codons 52, 54, and 57, and a functional promoter polymorphism at -221, were compared in a two-stage study of 337 patients with invasive pneumococcal disease and 1032 controls. All individuals were recruited from an ethnically homogeneous white population in Oxfordshire, UK. Patients had S pneumoniae isolated from a normally sterile site. Findings In our initial set of participants, 28 (12%) of 229 patients and 18 (5%) of 353 controls were homozygotes for MBL codon variants (odds ratio 2.59 [95% CI 1.39-4.83], p=0.002). Neither heterozygosity for these codon variants nor the promoter polymorphism was associated with susceptibility. In a confirmatory study, 11 (10%) of 108 patients were MBL homozygotes compared with 36 (5%) of 679 controls (p=0.046). Interpretation Homozygotes for MBL codon variants, who represent about 5% of north Europeans and north Americans and larger proportions of populations in many developing countries, could be at substantially increased risk of invasive pneumococcal disease.
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页码:1569 / 1573
页数:5
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