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Caucasian Controls (caucasian + control)
Selected AbstractsActivated monocytes and platelet-monocyte aggregates in patients with sickle cell disease*INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2002TED WUN Tumour necrosis factor-, (TNF-,) and interleukin-1, (IL-1,) increase endothelial surface receptors that mediate the adherence of sickle erythrocytes to the endothelium. Increased circulating levels of these cytokines have been found in patients with sickle cell disease (SCD). Monocytes are a source of both of these inflammatory mediators; we therefore determined whether circulating monocytes were activated in SCD, as defined by intracellular expression of these cytokines. Blood was also assayed for the presence of platelet,monocyte aggregates (PMAs), as platelet adherence is one possible mechanism for monocyte activation. The median percentages of monocytes expressing intracellular TNF-, and IL-1, in SCD patients were 6.8 (2.8,17.3) [median (range)] and 14.1 (1.3,44.8), respectively. In African-American controls the corresponding percentages were 0.3 (0.1,0.5) and 0.4 (0.1,3.0), and in Caucasians 0.2 (0.1,0.5) and 0.8 (0.8,1.9) (P < 0.001, Kruskal,Wallis). The mean percentage (± SD) of PMA was 14.0 ± 8.3 for Caucasian controls, 25.7 ± 7.3 for African-American controls, and 45.7 ± 21.6 for patients with SCD (P < 0.001, RM ANOVA; P < 0.05, Newman,Keuls posthoc test). We conclude that there are increased circulating PMAs and monocyte activation in patients with SCD. [source] No Association of the ACTN3 Gene R577X Polymorphism with Endurance Performance in Ironman TriathlonsANNALS OF HUMAN GENETICS, Issue 6 2007C. J. Saunders Summary Alpha-actinins are major structural components of the Z-discs in skeletal muscle. Alpha-actinin 3 is encoded by the ACTN3 gene and is expressed only in type II muscle fibres. Homozygosity for the nonsense mutation, 577X, within ACTN3 results in deficiency of ,-actinin-3 but does not result in an abnormal muscular phenotype. Previous research has found an association of the 577R allele with sprinting and/or power performance. It has also been suggested that the 577X allele may confer an advantage during endurance events. Four hundred and fifty seven Caucasian male triathletes who completed either the 2000 and/or 2001 226 km South African Ironman Triathlons, and 143 Caucasian controls, were genotyped for the R577X mutation within the ACTN3 gene. There were no significant differences in either the genotype (P = 0.486) or allele (P = 0.375) frequencies within the fastest, middle of the field or slowest Caucasian male finishers and the control population. In conclusion, the R577X polymorphism within the ACTN3 gene was not associated with ultra-endurance performance in the 2000 and 2001 South African Ironman Triathlons. [source] A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22,ARTHRITIS & RHEUMATISM, Issue 2 2010Hanneke J. M. Kerkhof Objective To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. Methods We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and ,39,000 controls. Meta-analyses were performed using the program Comprehensive Meta-analysis, with P values <1 × 10,7 considered genome-wide significant. Results The C allele of rs3815148 on chromosome 7q22 (minor allele frequency 23%; intron 12 of the COG5 gene) was associated with a 1.14-fold increased risk (95% confidence interval 1.09,1.19) of knee and/or hand OA (P = 8 × 10,8) and also with a 30% increased risk of knee OA progression (95% confidence interval 1.03,1.64) (P = 0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (68 kb upstream of GPR22), which is associated with GPR22 expression levels in lymphoblast cell lines (P = 4 × 10,12). Immunohistochemistry experiments revealed that G protein,coupled receptor protein 22 (GPR22) was absent in normal mouse articular cartilage or synovium. However, GPR22-positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged with in vivo papain treatment or methylated bovine serum albumin treatment. GPR22-positive chondrocyte-like cells were also found in osteophytes in instability-induced OA. Conclusion Our findings identify a novel common variant on chromosome 7q22 that influences susceptibility to prevalence and progression of OA. Since the GPR22 gene encodes a G protein,coupled receptor, this is potentially an interesting therapeutic target. [source] The shared epitope hypothesis in rheumatoid arthritis: Evaluation of alternative classification criteria in a large UK Caucasian cohortARTHRITIS & RHEUMATISM, Issue 5 2008Ann W. Morgan Objective Many classification systems for the HLA,DRB1 allelic association with rheumatoid arthritis (RA) have been reported, but few have been validated in additional populations. We sought to evaluate 3 different DRB1 allele classification systems in a large cohort of Caucasian RA patients and control subjects in the UK. Methods HLA,DRB1 typing was undertaken in 1,325 Caucasian RA patients and 462 healthy Caucasian controls who were residents of the UK. Logistic regression analyses were performed to investigate the different classification systems. Results We confirmed the association between the susceptibility alleles S2 and S3P, as proposed by Tezenas du Montcel, and the presence of RA in UK Caucasians. A significant hierarchy of risk was observed within the S3P allele group. There was no evidence of a significant association between DRB1*1001 and RA. Our data did not support the hypothesis that an isoleucine at position 67 conferred protection against RA, other than in contrast to the susceptibility alleles. However, the presence of an aspartic acid at amino acid 70 did appear to confer some degree of protection. Conclusion We were unable to fully substantiate any of the 3 recent revisions of the shared epitope hypothesis in this large cohort of Caucasian RA patients and control subjects in the UK. This reinforces the importance of evaluating disease susceptibility alleles in different Caucasian populations as well as in other ethnic groups. In particular, it will be important to clarify the precise DRB1 association in a given population before DRB1 genotyping is incorporated into clinical diagnostic or treatment algorithms. [source] Mutation screening of the macrophage migration inhibitory factor gene: Positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 9 2002Rachelle Donn Objective To determine if polymorphisms of the macrophage migration inhibitory factor (MIF) gene are associated with juvenile idiopathic arthritis (JIA). Methods Denaturing high-performance liquid chromatography was used to screen the MIF gene in 32 UK Caucasian controls and 88 UK Caucasian JIA patients. Ninety-two healthy UK Caucasian controls were then genotyped for each of the polymorphic positions identified. A panel of 526 UK Caucasian JIA patients and 259 UK Caucasian controls were subsequently genotyped for a single-nucleotide polymorphism (SNP) identified in the 5,-flanking region of the gene, using SNaPshot ddNTP primer extension and capillary electrophoresis. The functional significance of this polymorphism was also studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. Results A tetranucleotide repeat CATT(5,7) beginning at nucleotide position ,794 and 3 SNPs at positions ,173 (G to C), +254 (T to C), and +656 (C to G) of the MIF gene were identified. No JIA-specific mutations were found. Allele and genotype frequencies differed significantly between the controls and the JIA patients for the MIF-173 polymorphism. Individuals possessing a MIF-173*C allele had an increased risk of JIA (34.8% versus 21.6%) (odds ratio 1.9, 95% confidence interval 1.4,2.7; P = 0.0002). Furthermore, the MIF-173* G and C variants resulted in altered expression of MIF in a cell type,specific manner. Serum levels of MIF were also significantly higher in individuals who carried a MIF-173*C allele (P = 0.04). Conclusion The ,173-MIF*C allele confers increased risk of susceptibility to JIA. Our data suggest a cell type,specific regulation of MIF, which may be central to understanding its role in inflammation. [source] Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki diseaseCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2007W. B. Breunis Summary Kawasaki disease (KD) is an acute vasculitis occurring in young children. Its aetiology is unknown, but an infectious agent is assumed. Increased levels of proinflammatory cytokines and chemokines have been reported in KD. Genetic variation in these genes and the receptors for these genes could influence the regulation of cytokines and chemokines. In a case,control study of 170 Dutch Caucasian KD patients and 300 healthy Dutch Caucasian controls, common genetic variants in chemokine receptor genes CCR3, CCR2, CCR5, CX3CR1, CXCR1 and CXCR2 were analysed. Of the eight studied single nucleotide polymorphisms (SNPs) in the CCR3,CCR2,CCR5 gene cluster, four showed a significant association with susceptibility to KD. Moreover the CCR5 -,32 was observed with an allele frequency of 10·7% in the control population compared to 6·5% in the KD patients (P = 0·04). Two haplotypes of the CCR3,CCR2,CCR5 gene-cluster appear to be at risk haplotypes for KD and one a protective haplotype. No association was observed with the studied SNPs in CX3CR1, CXCR1 and CXCR2. In conclusion, in a Dutch cohort of KD patients an association of KD occurrence with common genetic variants in the chemokine receptor gene-cluster CCR3,CCR2,CCR5 was observed. [source] The influence of human leucocyte antigen (HLA) genes on autoimmune thyroid disease (AITD): results of studies in HLA-DR3 positive AITD familiesCLINICAL ENDOCRINOLOGY, Issue 1 2002Yoshiyuki Ban Summary objective Population-based, case,control studies have consistently shown association of Graves' disease (GD) with human leucocyte antigen (HLA)-DR3 in Caucasian populations. HLA association studies in Hashimoto's thyroiditis (HT) have also suggested an association with DR3, as well as with other HLA alleles. In contrast, HLA linkage studies in autoimmune thyroid disease (AITD) have been largely negative. The aim of the present study was to investigate the role of HLA in AITD and to explain the observed associations, but lack of linkage, by examining only AITD families with the associated allele, DR3. patients We studied 99 probands (60 with GD and 39 with HT) from 99 multiplex, multigenerational Caucasian AITD families, and 135 age- and sex-matched Caucasian controls in association studies. In addition, a dataset of 34 Caucasian AITD families (out of the 99 families) with HLA-DR3 positive probands were analysed in linkage studies. design HLA typing was performed using the technique of group-specific polymerase chain reaction-amplification with restriction enzyme digestion. Whole genome screening was performed using the ABI microsatellite panels. For fine mapping of the HLA region, we used the following markers: D6S276, D6S464, D6S439, D6S273, tumour necrosis factor , and D6S1610. LOD scores were calculated using the LIPED and GeneHunter programs. results Case,control association analyses using the probands from our 99 Caucasian families showed an association of GD with DRB1*03 [P = 0·00032, relative risk (RR) = 3·4]. Linkage analysis for the HLA region in the 34 DR3 positive AITD families showed negative LOD scores throughout the region. The two-point LOD score at marker D6S273 (the closest to HLA-DRB1) was ,3·0, and the multipoint LOD score was ,7·6, demonstrating strong evidence against linkage to the HLA region in the subset of DR3 positive families. Whole genome screening in the subset of 34 DR3 positive families revealed one locus showing evidence for linkage to AITD: D3S1580 on chromosome 3q27 with a maximum two-point LOD score of 2·1. conclusions The HLA locus did not cosegregate with disease in DR3 positive families, suggesting that HLA genes are not major genes for AITD expression even within DR3 positive families; Hence, although HLA-DR3 was associated with GD in the probands, it was most likely a modulating gene and not causative; and, as the DR3 positive families showed evidence for linkage with D3S1580, it may imply that the DR3 gene modulated the effect of a susceptibility gene within the D3S1580 locus. [source] | ||||||||||