Table 3.
NFKBIL2 and flanking gene polymorphism genotype frequencies in European individuals with IPD and controls
| Polymorphism/locationa (major/minor allele) | Status | Genotype distributionb | Genotypic 3 × 2 chi-square (P value) | Heterozygote protection modelc | |||
|---|---|---|---|---|---|---|---|
| AA | Aa | aa | OR (95% CI) | P valued | |||
| rs10448143, -5,224, 5' upstream (C/T) | Control | 203 (57.7%) | 126 (35.8%) | 23 (6.5%) | 1.245 (0.537) | 1.17 (0.79 to 1.72) | 0.425 |
| IPD | 88 (56.1%) | 62 (39.5%) | 7 (4.5%) | ||||
| rs2170096, -4,368, 5' upstream (C/G) | Control | 164 (24.3%) | 349 (51.7%) | 162 (24.0%) | 4.927 (0.085) | 0.71 (0.51 to 0.99) | 0.036 |
| IPD | 53 (26.4%) | 87 (43.3%) | 61 (30.3%) | ||||
| rs4925858, -3,771, 5' upstream (G/A) | Control | 185 (27.1%) | 360 (52.7%) | 138 (20.2%) | 6.664 (0.036) | 0.69 (0.50 to 0.95) | 0.016 |
| IPD | 66 (29.6%) | 97 (43.5%) | 60 (26.9%) | ||||
| rs760477, -263, NFKBIL2 intron 4 (C/T) | Control | 188 (26.3%) | 370 (51.7%) | 158 (22.1%) | 9.810 (0.007) | 0.64 (0.48 to 0.85) | 0.002 |
| IPD | 82 (31.3%) | 106 (40.5%) | 74 (28.2%) | ||||
| rs2306384, +2,754, Ser/Gly, NFKBIL2 exon 11 (A/G) | Control | 158 (24.6%) | 336 (52.4%) | 147 (22.9%) | 12.329 (0.002) | 0.61 (0.45 to 0.83) | 0.001 |
| IPD | 67 (27.0%) | 100 (40.3%) | 81 (32.7%) | ||||
| rs4082353, +12,589, NFKBIL2 intron 25 (G/T) | Control | 175 (27.2%) | 327 (50.8%) | 142 (22.0%) | 9.932 (0.007) | 0.66 (0.49 to 0.89) | 0.005 |
| IPD | 70 (28.6%) | 99 (40.4%) | 76 (31.0%) | ||||
| rs2272658, +16,899, VPS28 intron 4 (C/T) | Control | 156 (24.6%) | 330 (52.1%) | 147 (23.2%) | 6.684 (0.035) | 0.68 (0.49 to 0.95) | 0.023 |
| IPD | 47 (25.7%) | 78 (42.6%) | 58 (31.7%) | ||||
| rs13258200, +36,964, CPSF1 intron 2 (A/C) | Control | 258 (39.2%) | 317 (48.1%) | 84 (12.7%) | 0.364 (0.833) | 0.95 (0.72 to 1.26) | 0.739 |
| IPD | 107 (38.9%) | 129 (46.9%) | 39 (14.2%) | ||||
| rs4380978, +68,695, ADCK5 intron 1 (G/C) | Control | 212 (31.7%) | 347 (51.9%) | 110 (16.4%) | 0.227 (0.893) | 0.94 (0.70 to 1.26) | 0.696 |
| IPD | 78 (32.0%) | 123 (50.4%) | 43 (17.6%) | ||||
VPS28, vacuolar protein sorting 28; CPSF1, cleavage and polyadenylation-specific factor 1; ADCK5, aarF domain-containing kinase 5; OR, odds ratio; CI, confidence interval; IPD, invasive pneumococcal disease. The following NFKBIL2 SNPs were nonpolymorphic or very rare (minor allele frequency <0.01) in the UK Caucasian population studied: rs7459910; rs2306383; rs4448319; rs3802163; rs4925856; rs2242264; rs2620660; rs741970; rs4925857; rs6985339; rs2928378; rs12677973. aSNP positions listed are relative to the start of translation (in exon 5). bNumber of individuals (%). cComparison of heterozygotes [Aa] with homozygotes [AA + aa]. d2 × 2 chi-squared comparison, one degree of freedom. P values below 0.05 are highlighted in bold.