Host genetic risk factors for community-acquired pneumonia |
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Authors: | Lyubov E Salnikova Tamara V Smelaya Viktor V Moroz Arkady M Golubev Alexander V Rubanovich |
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Institution: | 1. N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin Street, Moscow 117971, Russia;2. V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences, 25 Petrovka Street, Build.2, Moscow 107031, Russia |
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Abstract: | This study was conducted to establish the contribution of genetic host factors in the susceptibility to community acquired pneumonia (CAP) in the Russian population. Patients with CAP (n = 334), volunteers without a previous history of CAP, constantly exposed to infectious agents, control A group (n = 141) and a second control group B consisted of healthy persons (n = 314) were included in the study. All subjects were genotyped for 13 polymorphic variants in the genes of xenobiotics detoxification CYP1A1 (rs2606345, rs4646903, and rs1048943), GSTM1 (Ins/del), GSTT1 (Ins/del), ABCB1 rs1045642); immune and inflammation response IL-6 (rs1800795), TNF-a (rs1800629), MBL2 (rs7096206), CCR5 (rs333), NOS3 (rs1799983), angiotensin-converting enzyme ACE (rs4340), and occlusive vascular disease/hyperhomocysteinemia MTHFR (rs1801133). Seven polymorphic variants in genes CYP1A1, GSTM1, ABCB1, NOS3, IL6, CCR5 and ACE were associated with CAP. For two genes CYP1A1 and GSTM1 associations remained significant after correction for multiple comparisons. Multiple analysis by the number of all risk genotypes showed a highly significant association with CAP (P = 2.4 × 10− 7, OR = 3.03, 95% CI 1.98–4.64) with the threshold for three risk genotypes. Using the ROC-analysis, the AUC value for multi-locus model was estimated as 68.38. |
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Keywords: | AIC Akaike information criterion AUC area under curve CAP community acquired pneumonia CI confidence interval CNV copy number variations Del (D) deletion FDR false discovery rate HWE Hardy&ndash Weinberg equilibrium HWP Hardy&ndash Weinberg probability Ins (I) insertion LD linkage disequilibrium OR odds ratio ROC receiver operating characteristic SE standard error Se sensitivity SNP single&ndash nucleotide polymorphism Sp specificity |
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