IL17RA gene variants and anti-TNF response among psoriasis patients.
Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.
Department of Dermatology II; Hospital Universitario Central Asturias; Oviedo, Spain.
A
A
Batalla
Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
E
E
Coto
Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
J
J
Gómez
Department of Dermatology II; Hospital Universitario Central Asturias; Oviedo, Spain.
N
N
Eirís
Department of Dermatology II; Hospital Universitario Central Asturias; Oviedo, Spain.
D
D
González-Fernández
Department of Dermatology II; Hospital Universitario Central Asturias; Oviedo, Spain.
C
C
Gómez-De Castro
Department of Dermatology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
E
E
Daudén
Department of Dermatology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
M
M
Llamas-Velasco
Department of Clinical Pharmacology, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
R
R
Prieto-Perez
Department of Clinical Pharmacology, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
F
F
Abad-Santos
Department of Dermatology, HU Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.
G
G
Carretero
Department of Immunology, HU Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.
F S
FS
García
Unidad Investigación HU Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.
Y B
YB
Godoy
Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
L F
LF
Cardo
Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
B
B
Alonso
Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
S
S
Iglesias
Department of Dermatology II; Hospital Universitario Central Asturias; Oviedo, Spain.
P
P
Coto-Segura
D000068879:Adalimumab / Q000627:therapeutic use; D000483:Alleles; D003430:Cross-Sectional Studies; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D020381:Interleukin-17 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics*; D053722:Receptors, Interleukin-17 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
C109985:IL17RA protein, human; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
J Exp Med. 2006 Nov 27;203(12):2577-87
17074928
Pharmacogenet Genomics. 2012 Feb;22(2):134-42
22158445
Cytokine. 2013 Dec;64(3):642-5
24084331
Hum Immunol. 2015 Mar;76(2-3):75-8
25636567
Scand J Gastroenterol. 2009;44(6):720-6
19263269
Pharmacogenomics. 2015;16(15):1723-31
26415694
Cytokine. 2013 Oct;64(1):58-61
23778030
Rheumatol Int. 2013 May;33(5):1165-76
22955875
Cytokine. 2013 Nov;64(2):477-85
24011563
Skin Therapy Lett. 2007 Sep;12(7):4-6
17940711
J Am Acad Dermatol. 2005 Aug;53(2):346-51
16021137
Transplantation. 2012 May 15;93(9):900-7
22377791
Mol Carcinog. 2013 Nov;52(11):871-8
22692973
J Cardiovasc Transl Res. 2014 Feb;7(1):133-7
24190697
Actas Dermosifiliogr. 2012 May;103(4):301-7
22188951
Am J Hum Genet. 2006 May;78(5):827-51
16642438
PLoS One. 2011;6(10):e26229
22028838
Rheumatol Int. 2008 Dec;29(2):173-8
18769923
J Invest Dermatol. 2010 May;130(5):1373-83
20032993
J Investig Allergol Clin Immunol. 2012;22(4):257-63
22812194
Annu Rev Pathol. 2012;7:385-422
22054142
Mol Diagn Ther. 2010 Apr 1;14(2):81-93
20359251
J Eur Acad Dermatol Venereol. 2016 Mar;30 Suppl 2:1-18
26812550
Nat Immunol. 2007 Sep;8(9):950-7
17676044
J Clin Immunol. 2008 Jan;28(1):44-9
17828618
Br J Dermatol. 2009 Feb;160(2):438-41
19016697
DNA Cell Biol. 2013 Oct;32(10):601-4
23905699
N Engl J Med. 2012 Mar 29;366(13):1251-2
22455420
J Biol Chem. 2013 Dec 6;288(49):35170-9
24145030
Circ J. 2014;78(12):2963-71
25342278
J Dermatol Sci. 2015 Nov;80(2):111-5
26347322
Ann Dermatol. 2012 Feb;24(1):61-5
22363157
Lancet. 2007 Jul 21;370(9583):263-71
17658397
J Allergy Clin Immunol. 2004 Dec;114(6):1265-73; quiz 1274
15577820
J Invest Dermatol. 2011 May;131(5):1003-5
21494239
J Immunol. 2001 Oct 15;167(8):4137-40
11591732
Br J Dermatol. 2014 Jul;171(1):97-107
24601997
J Invest Dermatol. 2009 Sep;129(9):2175-83
19295614
Hum Immunol. 2013 May;74(5):598-606
23220496
Gene. 2013 Feb 15;515(1):229-32
23219503
Autoimmunity. 2012 Nov;45(7):533-9
22816799
PLoS One. 2016 Jul 14;11(7):e0158905
27415816
Rheumatology (Oxford). 2009 Apr;48(4):367-70
19208686