MHC class I expression on human tumour cells and their susceptibility to NK lysis

Although natural killer (NK) activity is not restricted by the major histocompatibility complex (MHC), it has been suggested that the level of expression of MHC antigens by target cells may influence their lysis by NK cells. We have studied the NK susceptibility of 20 cell lines obtained from primitive and metastatic human tumours and the K562 cell line treated with gamma-interferon, phorbol ester TPA and tumour factor NK-RIF. When the levels of MHC class I antigen expression on the human tumour cell lines and their NK susceptibility were compared, no relationship between these two parameters was observed. Furthermore the treatment of K562 with either gamma-interferon, TPA or NK-RIF decreased its NK susceptibility independently of MHC class I expression. These results indicate that the MHC class I antigen is not the only factor directly involved in NK susceptibility and suggest that other membrane structures modulated by gamma-interferon, TPA or NK-RIF may also influence NK susceptibility.     

Effect of uremia and dialysis modality on mononuclear cell apoptosis

The aim of this study was to evaluate the effect of both uremia itself and hemodialysis (HD) membranes on the induction of apoptosis. Four groups of subjects were evaluated: 21 nondialyzed (Non-D) patients, 10 continuous ambulatory peritoneal dialysis (CAPD) patients, and 53 HD patients who were on hemophan, cuprophan, cellulose acetate, AN69, and polysulfone; control subjects were nine healthy volunteers. Circulating mononuclear cells were obtained before dialysis and cultured for 48 h. Mean percentage of apoptosis was analyzed by a FACScan flow cytometer using Annexin V-FITC. Cell apoptosis was increased in Non-D patients (11.5 +/- 5.5%) compared with control subjects (2.1 +/- 0.7%, P < 0.001) and CAPD patients (7. 0 +/- 5.8%, P < 0.05). In patients on HD with cuprophan, apoptosis was higher than in control subjects and Non-D and CAPD patients. In Non-D patients, apoptosis was inversely correlated with renal creatinine clearance (r = -0.62, P = 0.003). Cell apoptosis was higher in hemophan than the other HD membranes. In seven patients on hemophan, switching to polysulfone resulted in decreased apoptosis (P < 0.01). Mononuclear cell circulation through mini-dialyzers made of different types of membranes (cuprophan, hemophan, cellulose acetate, AN69, and polysulfone) prouced a significant increase in apoptosis. However, there was a marked difference in the percentage of apoptosis induced by these five membranes, being significantly increased in hemophan and cuprohan compared with the other three membranes. Similar results were obtained when whole blood from healthy donors was circulated through the mini-dialyzers, showing that mononuclear cell apoptosis was increased in hemophan and cuprophan compared with polysulfone. In conclusion, uremia and membrane characteristics may independently affect the mononuclear cell apoptosis.     

ABCC3 Polymorphisms and mRNA Expression Influence the Concentration of a Carboxylic Acid Metabolite in Patients on Clopidogrel and Aspirin Therapy

Acetylsalicylic acid (ASA) and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated. We investigated the relationship of ABC‐type efflux subfamily C member 3 (ABCC3) polymorphisms and mRNA expression with plasma concentrations of clopidogrel, salicylic acid (SA) and a carboxylic acid metabolite (CAM). Clopidogrel, CAM and SA plasma concentrations were measured simultaneously by liquid chromatography–tandem mass spectrometry (LCMS/MS) from 83 ACS patients undergoing percutaneous coronary intervention. ABCC3 (rs757421, rs733392 and rs739923) and CYP2C19*2 (rs4244285) polymorphisms as well as mRNA expression were evaluated. A positive correlation was found between CAM concentrations and ABCC3 mRNA expression (r = 0.494, p < 0.0001). Patients carrying genotype AA (rs757421 variant) had higher CAM concentrations and ABCC3 mRNA expression as compared to those of GG + GA carriers (p = 0.017). A multiple linear regression analysis revealed that ABCC3 mRNA expression (p = 0.017), rs757421 AA genotype (p = 0.001), blood collection time (p = 0.018) and clopidogrel dose (p = 0.001) contributed to the concentration of CAM. No associations were observed for the CYP2C19*2 polymorphism. These results suggest that up‐regulation of ABCC3 mRNA expression leads to increased plasma CAM levels through MRP3‐mediated cell efflux. The ABCC3 rs757421 polymorphism may contribute to gene expression. Therefore, ABCC3 may be a potential biomarker for the response to clopidogrel.     

DNA Commission of the International Society of Forensic Genetics: recommendations on forensic analysis using Y-chromosome short tandem repeats

During the past few years the DNA commission of the International Society of Forensic Genetics has published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. This latest report addresses a relatively new area, namely Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). This report addresses nomenclature, use of allelic ladders, population genetics and reporting methods.     

Autosomal STR genetic variation in negroid Chocó and Bogotá populations

Genetic data for eight autosomal STRs were obtained from two different population samples from Colombia: the European Mestizo population of Bogotá and the African descent population of the Chocó region. The STRs were analysed in a multiplex system that includes the STR markers CSF1PO, TPOX, TH01, VWA, D13S317, D7S820, D16S539 and D5S818. Separation of the fragments and fluorescent detection was carried out in an ABI 310 DNA sequencer and the typing was made by comparison with sequenced allelic ladders. Exact tests were used for testing linkage between the loci and for Hardy-Weinberg equilibrium. Significant differences were found between both populations for all the loci. Received: 30 May 2000 / Accepted: 20 March 2001     

Genetic profile characterization of 10 X-STRs in four populations of the southeastern region of Brazil

Ten X-chromosomal short tandem repeats (DXS8378, DXS9902, DXS7132, DXS9898, DXS6809, DXS6789, DXS7133, GATA172D05, GATA31E08 and DXS7423) were analyzed in four populations of the southeastern region of Brazil (São Paulo, Rio de Janeiro, Vitória and Belo Horizonte). No deviations from the Hardy–Weinberg equilibrium were observed for any of the analyzed loci in the four populations. The average diversity per locus varied between 68% for DXS8378, DXS7133, and DXS7423 and 83%, for DXS6809, with Rio de Janeiro being the most diverse population. Overall power of discrimination values in females varied between 0.99999999990 and 0.99999999997 and between 0.9999991 and 0.9999995 in males. These high values show the potential of this system for forensic application and relationships' testing in the studied groups. Genetic comparisons (exact tests of population differentiation and pairwise genetic distances) revealed significant differences between Brazilian and other populations from Europe, Latin America and Africa, as well as among different Brazilian populations.     

The Garífuna (Black Carib) people of the Atlantic coasts of Honduras: Population dynamics,structure, and phylogenetic relations inferred from genetic data,migration matrices,and isonymy

The aim of this study is to assess population dynamics, structure, and phylogenetic relations of the populations that inhabit the Caribbean coasts of Honduras: the Garífuna (or Black Carib) people, an admixture of Black Africans and Red Carib Native Amerindians. Thirteen autosomal tetranucleotide microsatellite markers of the DNA (namely short tandem repeats) were genotyped in samples from the Garifuna communities of Bajamar, in the Department of Cortés; Corozal, in the Department of Atlántida; and Iriona, in the Department of Gracias a Dios. Each subject in the study filled a questionnaire with the following information: complete name and surname of participant, and places of birth of the participant, his/her parents, and grandparents. We performed analyses that included determination of migration rates and residence patterns from information of places of birth, fixation indices from genetic data, and analysis of surnames of the sampled subjects (isonymy). Migration matrices showed a migration wave from east to west in the parents and grandparents of the subjects. A raise in migration rates and a shift in predominating residence pattern from neolocality to matrilocality from grandparents to parents were observed. Analysis of isonymy conjunctly with values for F_IS in each community showed high endogamy in Bajamar, and recent, high immigration in Iriona. A dendrogram constructed with allele frequencies of the Garifuna and other populations from the Americas, Africa, and Europe revealed the close relationships of this ethnic group with Afro‐Caribbean and African Populations. Am. J. Hum. Biol. 2010. © 2009 Wiley‐Liss, Inc.     

Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects

OBJECTIVE: The A allele of the PD1.3 single-nucleotide polymorphism (SNP) on the programmed cell death gene PDCD1 was markedly more frequent in patients with systemic lupus erythematosus (SLE) than in unaffected controls in a recent study involving large sets of Swedish, European American, and Mexican families. This study sought to determine the role of PDCD1 in susceptibility to SLE in the Spanish population. METHODS: Seven PDCD1 SNPs were studied in 518 SLE patients and 800 healthy control subjects who had been recruited in 5 distant towns spanning continental Spain. Patients and controls were of Spanish ancestry. The diagnosis of SLE was in accordance with the American College of Rheumatology updated classification criteria. RESULTS: The A allele of the PD1.3 polymorphism was significantly less frequent in Spanish female patients with SLE than in Spanish female controls (9.0% versus 13.0%, odds ratio 0.67, 95% confidence interval 0.50-0.89). This difference was consistent across the 5 sets of samples grouped by town of recruitment. The other PDCD1 SNPs were not associated with SLE susceptibility. The haplotype structure of PDCD1 in the Spanish controls was different from that reported in other healthy control populations. CONCLUSION: Our results confirm the association of PDCD1 with susceptibility to SLE, but the findings show a lack of involvement of the PD1.3 SNP, which is contrary to the role of the PD1.3 A allele observed previously. These contradictory results probably reflect population differences in the haplotype structure of the PDCD1 locus. More research focusing on new polymorphisms and identifying associations in other populations will be needed to clarify the role of PDCD1 in SLE susceptibility.