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Angra do Heroísmo, Portugal

Spinola H.,University of Madeira | Couto A.R.,SEEBMO | Couto A.R.,Institute for Molecular | Peixoto M.J.,SEEBMO | And 9 more authors.
Annals of Human Genetics

HLA class I diversity (loci A, B and C) was analysed in four populations, two from North Cameroon (Podokwo and Uldeme) and two from South Cameroon (Ewondo and Bamileke). Northern and southern Cameroon populations show a substantial genetic diversity in terms of haplotype sharing and genetic distances, even despite the low percentage of variance due to differences among populations evidenced by analysis of molecular variance. The signals of differentiation among populations are consistent with their linguistic affiliation, and support previous evidence, based on autosomal microsatellites and protein loci, which has shown that the complex pattern of genetic variation of Cameroon can in part be described by contrasting the northern and southern part of the country. Looking at our results in the more general framework of HLA diversity in sub-Saharan Africa, it turns out that the Podokwo and Uldeme show some genetic links to populations of the southern western branch of the Sahel corridor, while their high frequency of A*02 and C*04 alleles is congruent with previously hypothesised introgression of non-sub-Saharan alleles. On the other hand, signals of shared ancestry between the Bamileke and Ewondo and the Bantu speakers from central and southern Africa were detected. © 2011 The Authors, Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London. Source

Gruber B.L.,Mount Sinai School of Medicine | Couto A.R.,SEEBMO | Couto A.R.,University of Porto | Armas J.B.,SEEBMO | And 4 more authors.
Journal of Clinical Rheumatology

This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father. Copyright © 2012 by Lippincott Williams & Wilkins. Source

Mendes S.A.C.,University of The Azores | Mendes S.A.C.,University of Lisbon | Mansoor T.A.,University of Lisbon | Rodrigues A.,SEEBMO | And 4 more authors.

Two unprecedented guaiane-type sesquiterpene glycosides (undulatumosides A and B) were isolated by bioassay-guided fractionation from the MeOH extract of Pittosporum undulatum fruits, along with six known compounds, including the guaiane isomers 5-guaien-11-ol and 4-guaien-11-ol. The structures of the compounds were established as 4-guaiene-11-O-β-D-(3′-angeloxy- 6′-deoxy)-glucopyranoside and 1(5)-guaiene-11-O-β-D-(3′- angeloxy-6′-deoxy)-glucopyranoside by spectroscopic methods, including 1D and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY), and HRmass spectrometry. P. undulatum is a highly invasive weed that often outcompetes other plants, yet its fruits have become a traditional anti-inflammatory medicine in Azores. Therefore, aiming to investigate the claimed properties, the in vitro anti-inflammatory activity of guaiane-type sesquiterpenes was evaluated by analyzing their inhibitory effects on chemical mediators released by the LPS activated RAW 264.7 murine macrophages cell line. In addition, the cytotoxicity of these compounds was also evaluated in this cell line. Undulatumoside A, 5-guaien-11-ol and 4-guaien-11-ol displayed anti-inflammatory activity with IC50 values of 16.4, 8.1 and 7.2 μM, respectively, comparable to that of the positive control, indomethacin (IC50 = 18.2 μM), with no cytotoxic effects (IC 50≥198 μM). Furthermore, the same set of compounds was also assessed for anti-proliferative activity in lung large cell carcinoma COR-L23 and amelanotic melanoma C32 cells. © 2013 Elsevier Ltd. All rights reserved. Source

Bettencourt B.F.,SEEBMO | Bettencourt B.F.,IBMC Institute for Molecular and Cell Biology | Rocha F.L.,SEEBMO | Rocha F.L.,IBMC Institute for Molecular and Cell Biology | And 14 more authors.
Rheumatology (United Kingdom)

Objective. The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals.Methods. A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs).Results. ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10-3] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10-2), rs10050860 (OR = 0.7, P = 2.3 × 10-2), rs2287987 (OR = 0.6, P = 1.3 × 10-2). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10-3) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10-2). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10-2, OR = 1.3). No associations were observed in the TNFSF15 region.Conclusion. The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Source

Canhao H.,University of Lisbon | Canhao H.,Lisbon Academic Medical Center | Canhao H.,Brigham and Womens Hospital | Rodrigues A.M.,University of Lisbon | And 31 more authors.
BioMed Research International

Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results. No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion. This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response. Copyright © 2015 Helena Canhão et al. Source

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