0 1 A a DT 2 14 polymorphism polymorphism NN 15 19 that that WDT 20 27 affects affect VBZ 28 33 OCT-1 oct-1 NN 34 41 binding binding NN 42 44 to to TO 45 48 the the DT 49 52 TNF TNF NNP 53 61 promoter promoter NN 62 68 region region NN 69 71 is be VBZ 72 82 associated associate VBN 83 87 with with IN 88 94 severe severe JJ 95 102 malaria malaria NN 103 104 [ [ ( 104 107 see see VB 108 116 comments comment NNS 116 117 ] ] ) 119 126 Genetic genetic JJ 127 136 variation variation NN 137 139 in in IN 140 148 cytokine cytokine NN 149 157 promoter promoter NN 158 165 regions region NNS 166 168 is be VBZ 169 179 postulated postulate VBN 180 182 to to TO 183 192 influence influence VB 193 207 susceptibility susceptibility NN 208 210 to to TO 211 220 infection infection NN 220 221 , , , 222 225 but but CC 226 229 the the DT 230 239 molecular molecular JJ 240 250 mechanisms mechanism NNS 251 253 by by IN 254 259 which which WDT 260 264 such such JJ 265 278 polymorphisms polymorphism NNS 279 284 might might MD 285 291 affect affect VB 292 296 gene gene NN 297 307 regulation regulation NN 308 311 are be VBP 312 319 unknown unknown JJ 319 320 . . . 321 328 Through through IN 329 339 systematic systematic JJ 340 343 DNA dna NN 344 356 footprinting footprinting NN 357 359 of of IN 360 363 the the DT 364 367 TNF TNF NNP 368 369 ( ( ( 369 377 encoding encode VBG 378 384 tumour tumour NN 385 393 necrosis necrosis NN 394 400 factor factor NN 400 401 , , , 402 405 TNF TNF NNP 405 406 ) ) ) 407 415 promoter promoter NN 416 422 region region NN 422 423 , , , 424 426 we we PRP 427 431 have have VBP 432 442 identified identify VBN 443 444 a a DT 445 451 single single JJ 452 462 nucleotide nucleotide NN 463 475 polymorphism polymorphism NN 476 477 ( ( ( 477 480 SNP SNP NNP 480 481 ) ) ) 482 486 that that WDT 487 493 causes cause VBZ 494 497 the the DT 498 514 helix-turn-helix helix-turn-helix JJ 515 528 transcription transcription NN 529 535 factor factor NN 536 541 OCT-1 oct-1 NN 542 544 to to TO 545 549 bind bind VB 550 552 to to TO 553 554 a a DT 555 560 novel novel JJ 561 567 region region NN 568 570 of of IN 571 578 complex complex JJ 579 590 protein-DNA protein-dna JJ 591 603 interactions interaction NNS 604 607 and and CC 608 614 alters alter VBZ 615 619 gene gene NN 620 630 expression expression NN 631 633 in in IN 634 639 human human JJ 640 649 monocytes monocyte NNS 649 650 . . . 651 654 The the DT 655 668 OCT-1-binding oct-1-binding JJ 669 677 genotype genotype NN 677 678 , , , 679 684 found find VBN 685 687 in in IN 688 701 approximately approximately RB 702 703 5 5 CD 703 704 % % NN 705 707 of of IN 708 716 Africans African NNPS 716 717 , , , 718 720 is be VBZ 721 731 associated associate VBN 732 736 with with IN 737 745 fourfold fourfold RB 746 755 increased increase VBN 756 770 susceptibility susceptibility NN 771 773 to to TO 774 782 cerebral cerebral JJ 783 790 malaria malaria NN 791 793 in in IN 794 799 large large JJ 800 812 case-control case-control JJ 813 820 studies study NNS 821 823 of of IN 824 828 West west JJ 829 836 African african JJ 837 840 and and CC 841 845 East east JJ 846 853 African african JJ 854 865 populations population NNS 865 866 , , , 867 872 after after IN 873 883 correction correction NN 884 887 for for IN 888 893 other other JJ 894 899 known know VBN 900 903 TNF tnf NN 904 917 polymorphisms polymorphism NNS 918 921 and and CC 922 928 linked link VBN 929 932 HLA HLA NNP 933 940 alleles allele NNS 940 941 . . .