title: Systemic lupus erythematosus: association with KIR and SLC11A1 polymorphisms, ethnic predisposition and influence in clinical manifestations at onset revealed by ancestry genetic markers in an urban Brazilian population.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belém, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3'UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations.
authors.affiliation: 1Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil.
authors.forename: L S R A
authors.initials: LS
authors.lastname: Pedroza
authors.forename: M F L C
authors.initials: MF
authors.lastname: Sauma
authors.forename: J M
authors.initials: JM
authors.lastname: Vasconcelos
authors.forename: L Y C
authors.initials: LY
authors.lastname: Takeshita
authors.forename: E M
authors.initials: EM
authors.lastname: Ribeiro-Rodrigues
authors.forename: D
authors.initials: D
authors.lastname: Sastre
authors.forename: C M
authors.initials: CM
authors.lastname: Barbosa
authors.forename: J A B
authors.initials: JA
authors.lastname: Chies
authors.forename: T D
authors.initials: TD
authors.lastname: Veit
authors.forename: C P S
authors.initials: CP
authors.lastname: Lima
authors.forename: L F
authors.initials: LF
authors.lastname: Oliveira
authors.forename: B L
authors.initials: BL
authors.lastname: Henderson
authors.forename: A P G
authors.initials: AP
authors.lastname: Castro
authors.forename: M H T
authors.initials: MH
authors.lastname: Maia
authors.forename: F B
authors.initials: FB
authors.lastname: Barbosa
authors.forename: S E B
authors.initials: SE
authors.lastname: Santos
authors.forename: J F
authors.initials: JF
authors.lastname: Guerreiro
authors.forename: L
authors.initials: L
authors.lastname: Sena
authors.forename: E J M
authors.initials: EJ
authors.lastname: Santos
mesh_terms: D000328:Adult; D017668:Age of Onset; D001938:Brazil; D027682:Cation Transport Proteins / Q000235:genetics*; D002947:Cities; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics*; D054349:Receptors, KIR3DS1 / Q000235:genetics; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D005819:Genetic Markers; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1; D000099173:Natural Resistance-associated Macrophage Protein 1; C433932:KIR2DS2 protein, human; C531595:KIR2DS5 protein, human