Role of genetics in the diagnosis and prognosis of Crohn's disease

Table 1 Genetic polymorphisms related to Crohn’s disease

Diagnosis of CD
Innate pattern recognition receptors	NOD2/CARD15, OCTN, TLR
Epithelial barrier homeostasis	IBD5, DLG5
Molecular mimicry and autophagy	ATG16L1, IRGM, LRRK2
Lymphocyte differentiation	IL23R, STAT3
Secondary immune response and apoptosis	MHC, HLA
Prognosis of CD
Age of CD onset	TNFRSF6B, CXCL9, IL23R, NOD2, ATG16L1, CNR1, IL-10, MDR1, DLG5, IRGM
CD behavior
Stenotic/stricturing behavior	NOD2, TLR4, IL-12B, CX3CR1, IL-10, IL-6
Penetrating/fistulizing behavior	NOD2, IRGM, TNF, HLADRB1, CDKAL1
Inflammatory behavior	HLA
Granulomatous disease	TLR4/CARD15
CD location
Upper gastrointestinal	NOD2, MIF
Ileal	IL-10, CRP, NOD2, ZNF365, STAT3
Ileocolonic	ATG16L1, TCF-4 (TCF7L2)
Colonic	HLA, TLR4, TLR1, -2, -6
CD activity	HSP70-2, NOD2, PAI-1, CNR1
Surgery	NOD2, HLA-G
Dysplasia and cancer	FHIT
Extraintestinal manifestations	CARD15, FcRL3, HLADRB*103, HLAB*27 HLA-B*44, HLA-B*35, TNFα-308A, TNF-1031C, STAT3
Pharmacogenetics in CD	CARD15, NAT, TPMT, MDR1, MIF, DLG5, TNF, LTA

NOD: Nucleotide binding and oligomerization domain; CD: Crohn’s disease; LRR: Leucine-rich repeat; OCTN: Organic cation transporter; TLR: Toll-like receptor; DLG5: Discs large homolog 5; LTA: Lymphotoxin α; CARD: Caspase recruitment domain; STAT3: Signal transducer and activator of transcription 3; MHC: Major histocompatability complex; PAI-1: Type 1 plasminogen activator inhibitor; FHIT: Fragile histidine triad; NAT: N-acetyltransferase; MIF: Macrophage migration inhibition; HLA: Human leucocyte antigen; TPMT: Thiopurine methyltransferase; MDR1: Multidrug resistance gene 1; TNF-α: Tumour necrosis factor-α; Tcf: T-cell factor; Atg: Angiotensinogen; FCRL: Fc receptor-like; ZNF: Zinc finger; TNFRSF: Tumor necrosis factor receptor superfamily; IRGM: Immunity-related GTPase family, M; HLA: Human leukocyte antigen; LRRK2: Leucine-rich repeat kinase 2; CNR: Cadherin-related neuronal receptor.

Table 2 Predicted future developments in the genetics of Crohn’s disease

What lies ahead in the genetics of crohn’s disease
Gene-to-gene crosstalk and epistasis
Genome-wide association studies
Microarrays
Fine single nucleotide polymorphism analysis
Genetic consortium studies and genome-wide scans
Genome-wide association studies
Genetic consortium studies
Future perspectives
Functional studies to understand the mechanisms
Combining genetic data with functional data
Combination of a panel of clinical, biochemical, serological and genetic factors
Functional consequences of polymorphisms
Molecular and cellular mechanisms leading to Crohn’s disease
Predict disease outcomes
Redesigning the methods of treatment