Rheumatoid Arthritis in Latin Americans Enriched for Amerindian Ancestry Is Associated With Loci in Chromosomes 1, 12, and 13, and the HLA Class II Region

Abstract

Objective To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry. Methods Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software. Results A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA–DQB1– DQA2 (P = 7.6 × 10−10), with 3 independent effects. We identified an association in the PLCH2‐HES5‐TNFRSF14‐MMEL1 region of chromosome 1 (P = 9.77 × 10−6), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10−7). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10−6). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti–cyclic citrullinated peptide antibodies. Conclusion Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.

Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome

“…The OMRF IRB approved the study and all subjects provided written informed consent. Rheumatoid arthritis patients, mostly from South America and of Hispanic ethnicity, were collected and characterized as previously described [11]. All patients met recognized criteria for rheumatoid arthritis [10, 12].…”

ICP: A novel approach to predict prognosis of prostate cancer with inner-class clustering of gene expression data

“…They are TBP:HIP1, PTPN22:SPRED2, AR:MSMB, and MYH11:ACTA2. TBP:HIP1 is involved in transcription regulation process [47], PTPN22:SPRED2 is related to anti-cyclic citrullinated peptide antibodies [48], MSMB has indirect relationship with AR in transcription process [49], and MYH11:ACTA2 can cause TAAD (Thoracic Aortic Aneurysm/Dissection) [50,51].…”

Genética da artrite reumatoide: é necessário um novo impulso em populações latino‐americanas

“…49 Um estudo recente examinou o loci de susceptibilidade para a AR entre indivíduos da América Latina com uma ancestralidade genética ameríndia e europeia mista. 50 Esses estudos genotiparam 196.524 marcadores, cobriram o loci anteriormente associado a várias doenças autoimunes, em 1.475 pacientes com AR e 1.213 controles. Foi observada uma forte associação genética da AR com a região do MHC, com três efeitos independentes, provavelmente decorrente da origem diversa das amostras.…”