The characteristics of the host are extremely important when starting treatment
as pharmacogenomic properties determine the level and speed of drug metabolism
and thus the efficacy and the toxicity of the administered drugs. The genetic
variability of the gene for thiopurineS-methyltransferase (TPMT) is such an
example as it determines the dosage range of azathioprine and 6-mercaptopurine,
two important drugs used in the treatment of inflammatory bowel disease. The role
of the TPMT protein is to inactivate the active metabolite of azathioprine,
6-thioguanine. In patients with genetic variants that decrease the functionality of
the protein (affects 11 % of the population), initiating standard doses of the drug can
lead to toxic side effects (myelosuppression, leucopenia).^8 By determining slow
metabolizers prior to initiating the therapy and correcting the drug dosage, lower
incidence of leucopenia has been achieved.^9
Immunological mechanisms are important in the development of secondary
resistance to biological therapy. Clinically it is difficult to differentiate it from the
secondary resistance due to reduced medication bioavailability. Understanding the
etiology of secondary resistance is of paramount importance for further treatment
since in the first case the continued use of the same drug is futile, while in the
second case the increase of the dosage can restore the response to therapy. Deter-
mining the serum drug level and the presence of antimedication antibodies (indi-
vidualized approach) can solve the dilemma.^10
A similar interplay of complex cellular interactions is an important determinant
in the pathophysiology of GI malignancies. The sequence of unregulated activation
of protooncogenes and inactivation of tumor suppressor genes in tumor stem cells is
the pathogenetic basis of the adenoma-carcinoma sequence.^11 Screening relatives
of patients suffering from familial adenomatous polyposis or hereditary
nonpolyposis colorectal cancer is a method that allows the early detection or
Table 1 Serological markers in inflammatory bowel disease
Antibody Antigen Control (%) CD (%) UC (%)
pANCA Histon H1 < 5 10–25 50–65
ASCA S. cervisiae 5 55–65 5
Anti-OmpC E. coli < 5 38–50 2
Anti-I2 P. fluorescens < 5542
Anti-flagelin Cbir-1 8–14 50 6
Anti-ALCA IgG Laminaribioside 2 27 9
Anti-ACCA IgA Chitobioside 12 25 25The occurrence of distinct antibodies in patients suffering from Crohn’s disease (CD), ulcerative
colitis (UC), and healthy controls (control) (modified from Mendoza and Abreu 2009 ).
(^8) Weinshilboum and Sladek ( 1980 ).
(^9) Coenen et al. ( 2014 ).
(^10) Panaccione and Ghosh ( 2010 ).
(^11) Markowitz and Bertagnolli ( 2009 ).
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