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.

Association of killer cell immunoglobulin-like receptor polymorphisms with chronic hepatitis C and responses to therapy in Brazil

“…The control sample consisted of 345 healthy unrelated individuals, representative of the same population as the patients. The control sample was the same as the one used in a previous study from our group (Pedroza et al , 2011). The mean age and proportion of females were, respectively, 41.7 years and 59% in controls, and 57.4 years and 40% in patients.…”

Association between killer cell immunoglobulin-like receptor (KIR) polymorphisms and systemic lupus erythematosus (SLE) in populations

“…All studies were case-control studies that investigated the association of KIR polymorphisms and susceptibility to SLE. Among the 10 articles, 3 [12,22,23] were Caucasians, 6 [24–28] were East Asians, 1 [29] was South Americans. Owning to the insufficient sample populations available for the South American group, we conducted ethnicity-specific meta-analyses for Caucasian and Asian populations.…”

“…Characteristics of the included studies are summarized in Table 1. Six [21,22,24,25,28,29] of 10 studies were of high quality (NOS score ≥7) and the other 4 studies were defined as moderate quality (all scored 6), which are shown in Table 1. [12,22–30] …”

Association of the CYP2B6 gene with anti-tuberculosis drug-induced hepatotoxicity in a Brazilian Amazon population

“…The method of genomic control employed in this study has been used successfully in other publications by this research group. 24,[29][30][31][32][33] The results from the multivariate statistical model used to determine the association between the CYP3A5 gene A6986G polymorphism and the drugs examined did not differ between the patients with and without hepatotoxicity (p = 0.176; OR 0.562, 95% CI 0.255-1.238). The CYP3A5 gene polymorphism results are consistent with data published previously for other populations, because no association was observed between the A6986G polymorphism and drug-induced hepatotoxicity.…”