Table 4.
Impact of COX-2 variants on malaria and SMA over 36 months
| Variants | Malaria | SMA | ||||||
|---|---|---|---|---|---|---|---|---|
| Events | RR | 95% CI | P value | Events | RR | 95% CI | P value | |
| −512 | ||||||||
| CC | n = 4591 | REF | – | – | n = 213 | REF | – | – |
| CT | n = 759 | 1.074 | 0.988–1.169 | 0.095 | n = 39 | 1.241 | 0.847–1.817 | 0.268 |
| TT | n = 109 | 1.072 | 0.866–1.329 | 0.522 | n = 6 | 1.088 | 0.449–2.637 | 0.852 |
| −608 | ||||||||
| TT | n = 3776 | REF | – | – | n = 184 | REF | – | – |
| TC | n = 1453 | 1.017 | 0.952–1.087 | 0.622 | n = 64 | 0.875 | 0.638–1.198 | 0.405 |
| CC | n = 230 | 0.746 | 0.640–0.869 | 1.811e−4 | n = 10 | 0.644 | 0.300–1.383 | 0.259 |
| −765 | ||||||||
| GG | n = 2290 | REF | – | – | n = 105 | REF | – | – |
| GC | n = 2322 | 0.980 | 0.919–1.045 | 0.537 | n = 1127 | 1.147 | 0.857–1.536 | 0.356 |
| CC | n = 847 | 1.035 | 0.943–1.136 | 0.466 | n = 26 | 0.654 | 0.397–1.076 | 0.095 |
| −1195 | ||||||||
| AA | n = 4963 | REF | – | – | n = 231 | REF | – | – |
| AG | n = 432 | 0.919 | 0.828–1.020 | 0.110 | n = 25 | 1.060 | 0.689–1.632 | 0.791 |
| GG | n = 64 | 0.798 | 0.615–1.035 | 0.089 | n = 2 | 0.303 | 0.042–2.168 | 0.235 |
| Haplotypes | ||||||||
| CTGA | n = 2390 | 1.077 | 0.987–1.174 | 0.096 | n = 123 | 1.464 | 0.971–2.207 | 0.069 |
| CCGA | n = 1411 | 1.017 | 0.939–1.101 | 0.682 | n = 64 | 1.085 | 0.743–1.584 | 0.674 |
| CTCA | n = 2140 | 1.026 | 0.952–1.105 | 0.508 | n = 99 | 1.049 | 0.746–1.477 | 0.782 |
| CTCG | n = 45 | 1.227 | 0.885–1.701 | 0.219 | n = 0 | – | – | – |
| TTCA | n = 676 | 1.115 | 1.013–1.227 | 0.026 | n = 38 | 1.320 | 0.842–2.068 | 0.226 |
| TTGG | n = 34 | 1.755 | 1.170–2.634 | 0.007 | n = 4 | 8.706 | 2.633–28.790 | 3.917e−4 |
| CCCA | n = 147 | 0.867 | 0.716–1.050 | 0.144 | n = 2 | 0.633 | 0.192–2.085 | 0.452 |
| TTGA | n = 113 | 1.032 | 0.842–1.265 | 0.763 | n = 3 | 0.830 | 0.259–2.664 | 0.754 |
| CTGG | n = 354 | 0.856 | 0.760–0.965 | 0.011 | n = 19 | 0.965 | 0.563–1.654 | 0.897 |
| TCGA | n = 16 | 0.670 | 0.401–1.119 | 0.126 | n = 0 | – | – | – |
| CCGG | n = 26 | 0.991 | 0.666–1.474 | 0.962 | n = 0 | – | – | – |
| TTCG | n = 31 | 1.608 | 1.091–2.371 | 0.016 | n = 4 | 5.714 | 1.725–18.930 | 0.004 |
Data are presented as relative risk (RR) and 95% confidence intervals (CI) determined using Poisson regression modeling performed on longitudinal data of >14,000 patient visits to assess the risk to malaria or SMA episodes. Children (n = 1081) were followed at day 14 after enrollment and 14 days after a malaria episode, quarterly, and at acute febrile visits for 36 months. There were 5,331 malaria episodes and 238 SMA (Hb < 5.0 g/dL) episodes. The log linear regression model controlled for age, sex, HIV-1 and bacteremia (presence/absence), and sickle cell trait, α+-thalassemia, and G6PD status. The homozygous wild-type genotypes and non-carriers of haplotypes were used as references in the analyses. Bold indicates a P value ≤ 0.050