Pharmacogenetics in inflammatory bowel disease: understanding treatment response and personalizing therapeutic strategies

Figures & data

Table 1 Drug-related markers in inflammatory bowel disease

Pharmacological group	Drug-related markers	Clinical utility
5-ASA	PPAR-α, PPAR-γ	Severity of inflammation in UC
	Hsp10, Hsp60, and Hsp90	Response to 5-ASA therapy
Corticosteroids	MDR1	Response to medical treatment
	GRβ	Nonresponder to steroids
	RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) SNPs	Steroid dependent
	IL-18 mucosal expression	Responder to steroids
Thiopurines	TPMT mutant alleles	TPMT deficiency associated with adverse events (myelotoxicity)
	HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype	Associated with adverse event (pancreatitis)
	Deletion of GST polymorphisms	Lack of adverse event
	TPMT activity, 6-TGN, 6-MMP levels	Adjust dose and therapeutic levels for reducing the risk of toxicity
Anti-TNF therapy	Caspase-9 TT genotype and Fas ligand-843 CC/CT genotype	Responder to anti-TNF therapy
	ATG16L1 TT genotype	Responder to adalimumab
	IL-23R SNPs: AA genotype for rs1004819, rs10889677, and rs11209032, GG genotype for rs2201841, and CC genotype for rs1495965	Responders to infliximab
	IL-1RN (rs4251961) allele C	Poor responder to anti-TNF therapy
	Measurement of anti-TNF serum levels and drug antibodies	Optimize anti-TNF treatment and identify nonresponders
Anti-integrin therapy	Granzyme A and αE integrin gene and protein expression	Responders to etrolizumab

Abbreviations: SNPs, single nucleotide polymorphisms; PPAR, peroxisome proliferator-activated receptors; 5-ASA, 5-aminosalicylic acid; IL, interleukin; Hsp, heat shock protein; MDR, multidrug resistant; TNF, tumor necrosis factor; GRβ, glucocorticoid receptor β; TPMT, thiopurine methyltransferase; HLA, human leukocyte antigen; GST, glutathione-S-transferase; 6-TGN, 6-thioguanine nucleotide; 6-MMP, 6-methylmercaptopurine; ATG16L1, autophagy-related 16-like 1; UC, ulcerative colitis.

Figure 1 Optimization of anti-TNF agents according drug serum levels and anti-drug antibodies

Abbreviation: TNF, tumor necrosis factor.