Impact of the IL-17F, IL-23 and IL-23R on susceptibility and phenotype of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a disease characterized by excessive proinflammatory cytokine production and damage to multiple organ systems. To investigate the potential association between cytokine gene polymorphisms and SLE, we performed a case-control study based on Polish population. SLE patients and controls, were examined for IL-23A rs11171806 G/A and IL-23R (rs1884444 G/T, rs10489629 G/A) by TaqMan SNP genotyping assay, for IL-17F rs763780 A/G and rs2397084A/G using the PCR- RFLP method. An increased frequency of AG genotype as well as G allele of the IL-17F rs763780 was found in patients with SLE, as compared with healthy subjects (OR = 3.947; p = 0.001 and OR = 3.538; p = 0.002, respectively). Frequencies of the rs1884444 TT genotype (OR = 138.1) and the rs1884444 T allele (OR = 2.176) were also higher in SLE patients (both p < 0.0001). Overall, weak LD was observed between the IL-17F rs763780 A/G and rs2397084 A/G polymorphisms (D'-0.003, r2- 0.000). From four possible haplotypes, frequencies of AG showed differences between both examined groups (p < 0.0001). We also observed a weak LD between the IL-23R rs10489629G/A and rs1884444 G/T (D'-0.199, r2-0.026). The genotype-phenotype analysis showed significant association between the IL-17F rs2397084 and mean value of the hemoglobin (p = 0.01), the IL-17F rs763780 and age (p = 0.008) and lupus anticoagulant (p = 0.09), the IL-23 rs11171806 and urea (p = 0.08) and C3 complement (p = 0.03), and the IL-23R rs1884444 G/T and activated partial thromboplastin time (p = 0.06). Present findings indicated that IL-17F rs763780 A/G and IL-23R rs1884444 G/T polymorphisms may be involved in susceptibility to SLE in the Polish population.
a Department of Biochemistry and Molecular Biology , National Institute of Geriatrics, Rheumatology and Rehabilitation , Warsaw , Poland.
Agnieszka
A
Paradowska-Gorycka
b Department of Computer Science and Statistics , Poznan University of Medical Sciences , Poznan , Poland.
Anna
A
Sowinska
a Department of Biochemistry and Molecular Biology , National Institute of Geriatrics, Rheumatology and Rehabilitation , Warsaw , Poland.
Barbara
B
Stypinska
c Department of Biochemistry and Molecular Biology , Poznan University of Medical Sciences , Poznan , Poland.
Malwina Katarzyna
MK
Grobelna
d Department of Connective Tissue Diseases , National Institute of Geriatrics, Rheumatology and Rehabilitation , Warsaw , Poland , and.
Marcela
M
Walczyk
d Department of Connective Tissue Diseases , National Institute of Geriatrics, Rheumatology and Rehabilitation , Warsaw , Poland , and.
Marzena
M
Olesinska
c Department of Biochemistry and Molecular Biology , Poznan University of Medical Sciences , Poznan , Poland.|e Mossakowski Medical Research Centre, Polish Academy of Sciences , Warsaw , Poland.
Piotr
P
Piotrowski
c Department of Biochemistry and Molecular Biology , Poznan University of Medical Sciences , Poznan , Poland.
Paweł Piotr
PP
Jagodziński
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D053759:Interleukin-23 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D012306:Risk; D055815:Young Adult
D001323:Autoantibodies; D015415:Biomarkers; C515500:IL23R protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D018123:Receptors, Interleukin
Association study; SLE; cytokine; pathogenesis; polymorphisms