Clinical relevance of advances in genetics and pharmacogenetics of IBD Tariq Ahmad, Cyrus Pesi Tamboli, Derek Jewell, Jean-Frédéric Colombel  Gastroenterology  Volume 126, Issue 6, Pages 1533-1549 (May 2004) DOI: 10.1053/j.gastro.2004.01.061

Figure 1 IBD linkage areas. Modified from Ahmad et al.65 Gastroenterology 2004 126, 1533-1549DOI: (10.1053/j.gastro.2004.01.061)

Figure 2 Structure of the CARD15 gene and location of the CD-associated variants. The numbers represent the amino acid position. NBD, nucleotide binding domain; LRR, leucine-rich repeat. Gastroenterology 2004 126, 1533-1549DOI: (10.1053/j.gastro.2004.01.061)

Figure 3 Genetic concepts of IBD. Reprinted with permission from Simmons and Orchard.88 Gastroenterology 2004 126, 1533-1549DOI: (10.1053/j.gastro.2004.01.061)

Figure 4 Population attributable risk (PAR) (%) of the 3 common CD-associated CARD15 variants, the HLA region, and other loci in patients with CD according to disease location. Modified and reprinted with permission from Ahmad et al.16 Gastroenterology 2004 126, 1533-1549DOI: (10.1053/j.gastro.2004.01.061)

Figure 5 AZA metabolism. Oral AZA is converted rapidly to 6-MP by a nonenzymatic process. Three enzymes then compete to metabolize 6-MP: XO, TPMT, and hypoxanthine-guanine phosphoribosyltransferase. Once formed, 6 thio-inosine monophosphate (6-TIMP) may be transformed in active 6-thioguanine nucleotides by the rate-limiting inosine monophosphate dehydrogenase (IMPDH) or methylated into 6-methyl-mercaptopurine ribonucleotides (6-MMPR). Gastroenterology 2004 126, 1533-1549DOI: (10.1053/j.gastro.2004.01.061)

Figure 6 Delay (in months) between the first administration of AZA/6-MP and the occurrence of bone marrow toxicity in 41 patients developing severe myelosuppression during AZA therapy. Patients classified as low methylator (LM) (n = 4) were homozygous for 1 nonfunctional mutation or heterozygous for 2 nonfunctional mutations, patients classified as intermediate methylator (IM) (n = 7) were heterozygous for 1 nonfunctional mutation, patients classified as high methylator (HM) (n = 29) were homozygous for the wild-type or heterozygous for 2 functional alleles. One patient not represented was heterozygous for a previously unknown mutation. Reprinted with permission from Colombel et al.112 Gastroenterology 2004 126, 1533-1549DOI: (10.1053/j.gastro.2004.01.061)