title: Polymorphisms in STK17A gene are associated with systemic lupus erythematosus and its clinical manifestations.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disorder with several clinical manifestations. SLE etiology has a strong genetic component, which plays a key role in disease's predisposition, as well as participation of environmental factors, such and UV light exposure. In this regard, we investigated whether polymorphisms in STK17A, a DNA repair related gene, encoding for serine/threonine-protein kinase 17A, are associated with SLE susceptibility. A total of 143 SLE patients and 177 healthy controls from Southern Brazil were genotyped for five STK17A TagSNPs. Our results indicated association of rs7805969 SNP (A and G/A genotype, OR=1.40 and OR=1.73, respectively) with SLE predisposition and the following clinical manifestations: arthritis, cutaneous and immunological alterations. When analyzing haplotypes distribution, we found association between TGGTC, TAGTC and AAGAT haplotypes and risk to develop SLE. When considering clinical manifestations, the haplotypes TGGTT and TAGTC were associated with protection against cutaneous alterations and the haplotype TAGTC to hematological alterations. We also observed association between SLE clinical manifestations and ethnicity, with the European-derived patients being more susceptible to cutaneous and hematological alterations.
authors.affiliation: Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Andréia Maria
authors.initials: AM
authors.lastname: da Silva Fonseca
authors.forename: Jaqueline
authors.initials: J
authors.lastname: de Azevedo Silva
authors.forename: João Alexandre Trés
authors.initials: JA
authors.lastname: Pancotto
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Donadi
authors.forename: Ludovica
authors.initials: L
authors.lastname: Segat
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.forename: Paula
authors.initials: P
authors.lastname: Sandrin-Garcia
mesh_terms: D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D017346:Protein Serine-Threonine Kinases; C115488:STK17A protein, human
keywords: ACR; APS; American College of Rheumatology Classification Criteria; CTLA-4; DAP protein kinase related apoptosis-inducing kinase 1; DNA; DNA PKs; DNA dependent protein kinase catalytic subunit; DNA repair of double strand breaks; DRAK1; DSBs; GWAS; IRF5; ITGAM; LD; MAF; PDCD-1; PTPN2; ROS; SLE; SNP; STAT4; STK17A; Serine/threonine protein kinase 17A; Single nucleotide polymorphisms; Systemic lupus erythematosus; UV; X-ray repair cross complementing group 1; X-ray repair cross complementing group 3; X-ray repair cross complementing group 4; XRCC1; XRCC3; XRCC4; antibody antiphospholipid; cytotoxic t-lymphocyte antigen 4; deoxyribonucleic acid; genome wide association studies; integrin alpha M; interferon regulatory factor 5; linkage disequilibrium; minor allele frequency; programmed cell-death 1; protein tyrosine phosphatase nonreceptor 22; reactive oxygen species; serine/threonine protein kinase 17A; signal transducer and activator of transcription 4; single nucleotide polymorphisms; systemic lupus erythematosus; ultra violet