Pharmacogenomics of infliximab therapy, impact of TNFRSF1A and
TNFRSF1B gene polymorphisms

J 2013

Pharmacogenomics of infliximab therapy, impact of TNFRSF1A and TNFRSF1B gene polymorphisms

KOLORZ, Michal; Katerina WROBLOVA; Jana MOKRANOVA; Ladislava BARTOSOVA; Petr DITE et al.

Základní údaje

Originální název

Pharmacogenomics of infliximab therapy, impact of TNFRSF1A and TNFRSF1B gene polymorphisms

Autoři

KOLORZ, Michal; Katerina WROBLOVA; Jana MOKRANOVA; Ladislava BARTOSOVA; Petr DITE; Vladimír ZBOŘIL a Milan BARTOS

Vydání

Biomedical Papers, Olomouc: Palacky University, Olomouc, Palacky University, 2013, 1213-8118

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30000 3. Medical and Health Sciences

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 1.661

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/13:00072502

Organizační jednotka

Lékařská fakulta

UT WoS

000324728600007

Klíčová slova anglicky

infliximab; single nucleotide polymorphism; pharmacogenomics; TNFR

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 4. 3. 2014 17:32, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

Introduction. Anti-TNF alpha monoclonal antibodies present an effective way of treating Crohn's disease ( CD). Despite their high benefits, there is about 30% rate of a primary non-response. The main target of infliximab is the soluble form of TNF alpha, which blocks its pro-inflammatory activity and the induction of apoptosis via the TNF alpha membrane form. The activity of TNF alpha and balance between its pro-inflammatory and pro-apoptotic effect is mediated by the interaction with its receptors (TNFR). Mechanisms of signaling via TNF alpha-TNFR interaction has been recently intensively studied from a perspective of selecting appropriate candidates for the infliximab treatment. Aim. The aim of this study was to evaluate whether polymorphisms in TNFRSF1A and TNFRSF1B genes influence the efficacy of the infliximab therapy. Methods. A total of 116 Caucasian CD patients treated with infliximab were genotyped. After initial 10 weeks of the infliximab therapy, effectiveness was determined and patients were divided into responders (n=98) and non-responders (n=18). Genotypes TNFRSF1A (T4672G, G3794C) and TNFRSF1B (T11695C, T587G) were determined by PCR-RFLP. Results. Frequencies of variant alleles of TNFRSF1A were comparable between responders and non-responders. Variant allele TNFRSF1B 11695C was more common in non-responders (41.7% vs. 30.1%). Similarly, the frequency of TNFRSF1B 587G allele in non-responders was 33.3% vs. 18.9% in responders. Homozygotes for variant alleles of TNFRSF1B 11695C were found more often (P=0.013; OR 5.89, CI 95% 1.6-22.1) in non-responders (n=5, 27.8%) than in responders (n=6, 6.1%). Our results imply that TNFRSF1B 11695C variant allele is associated with a low therapeutic effect of infliximab.

Citovat

KOLORZ, Michal; Katerina WROBLOVA; Jana MOKRANOVA; Ladislava BARTOSOVA; Petr DITE; Vladimír ZBOŘIL a Milan BARTOS. Pharmacogenomics of infliximab therapy, impact of TNFRSF1A and TNFRSF1B gene polymorphisms. Biomedical Papers, Olomouc: Palacky University. Olomouc: Palacky University, 2013, roč. 157, Supplementum 1, s. "S75"-"S78", 4 s. ISSN 1213-8118.

@article{1168328,
   author = {Kolorz, Michal and Wroblova, Katerina and Mokranova, Jana and Bartosova, Ladislava and Dite, Petr and Zbořil, Vladimír and Bartos, Milan},
   article_location = {Olomouc},
   article_number = {Supplementum 1},
   keywords = {infliximab; single nucleotide polymorphism; pharmacogenomics; TNFR},
   language = {eng},
   issn = {1213-8118},
   journal = {Biomedical Papers, Olomouc: Palacky University},
   title = {Pharmacogenomics of infliximab therapy, impact of TNFRSF1A and TNFRSF1B gene polymorphisms},
   volume = {157},
   year = {2013}
}

TY  - JOUR
ID  - 1168328
AU  - Kolorz, Michal - Wroblova, Katerina - Mokranova, Jana - Bartosova, Ladislava - Dite, Petr - Zbořil, Vladimír - Bartos, Milan
PY  - 2013
TI  - Pharmacogenomics of infliximab therapy, impact of TNFRSF1A and TNFRSF1B gene polymorphisms
JF  - Biomedical Papers, Olomouc: Palacky University
VL  - 157
IS  - Supplementum 1
SP  - "S75"-"S78"
EP  - "S75"-"S78"
PB  - Palacky University
SN  - 12138118
KW  - infliximab
KW  - single nucleotide polymorphism
KW  - pharmacogenomics
KW  - TNFR
N2  - Introduction. Anti-TNF alpha monoclonal antibodies present an effective way of treating Crohn's disease ( CD). Despite their high benefits, there is about 30% rate of a primary non-response. The main target of infliximab is the soluble form of TNF alpha, which blocks its pro-inflammatory activity and the induction of apoptosis via the TNF alpha membrane form. The activity of TNF alpha and balance between its pro-inflammatory and pro-apoptotic effect is mediated by the interaction with its receptors (TNFR). Mechanisms of signaling via TNF alpha-TNFR interaction has been recently intensively studied from a perspective of selecting appropriate candidates for the infliximab treatment. Aim. The aim of this study was to evaluate whether polymorphisms in TNFRSF1A and TNFRSF1B genes influence the efficacy of the infliximab therapy. Methods. A total of 116 Caucasian CD patients treated with infliximab were genotyped. After initial 10 weeks of the infliximab therapy, effectiveness was determined and patients were divided into responders (n=98) and non-responders (n=18). Genotypes TNFRSF1A (T4672G, G3794C) and TNFRSF1B (T11695C, T587G) were determined by PCR-RFLP. Results. Frequencies of variant alleles of TNFRSF1A were comparable between responders and non-responders. Variant allele TNFRSF1B 11695C was more common in non-responders (41.7% vs. 30.1%). Similarly, the frequency of TNFRSF1B 587G allele in non-responders was 33.3% vs. 18.9% in responders. Homozygotes for variant alleles of TNFRSF1B 11695C were found more often (P=0.013; OR 5.89, CI 95% 1.6-22.1) in non-responders (n=5, 27.8%) than in responders (n=6, 6.1%). Our results imply that TNFRSF1B 11695C variant allele is associated with a low therapeutic effect of infliximab.
ER  -

KOLORZ, Michal; Katerina WROBLOVA; Jana MOKRANOVA; Ladislava BARTOSOVA; Petr DITE; Vladimír ZBOŘIL a Milan BARTOS. Pharmacogenomics of infliximab therapy, impact of TNFRSF1A and TNFRSF1B gene polymorphisms. \textit{Biomedical Papers, Olomouc: Palacky University}. Olomouc: Palacky University, 2013, roč.~157, Supplementum 1, s.~''S75''-''S78'', 4 s. ISSN~1213-8118.

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