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UK Caucasian Population (uk + caucasian_population)

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Medical Sciences	100%

Selected Abstracts

Inflammatory bowel disease is linked to 19p13 and associated with ICAM-1

INFLAMMATORY BOWEL DISEASES, Issue 3 2004
Jin Hong Low
Abstract Genome-wide scans have implicated several susceptibility loci, but linkage of 19p13 (IBD6) to Crohn's disease (CD) has not been fully replicated. We report a replication study of IBD6 in a UK Caucasian population. Two hundred eighty-four affected sibling pairs from 234 families were used for the linkage study. Linkage between IBD6 linkage and CD was replicated (LOD score = 1.59). Two candidate genes (DDXL and ICAM-1) within the IBD6 locus were examined in a case/control study with a total of 228 CD and 243 ulcerative colitis (UC) patients and 407 healthy controls. No association to either UC or CD was found in three novel intronic single nucleotide polymorphisms (SNPs) in DDXL. For ICAM-1, a significant association was found between K469 homozygosity and CD overall (39.9% vs 29.4%; Pc = 0.0096) and between E469 and fistulating disease (21.8% vs 10.0%, Pc = 0.030). In the UC group, limited disease extent was associated with homozygosity of the G241 allele (82.7% vs 64.7%, Pc = 0.0040). These data support linkage for CD at 19p13 and suggest that the amino acid polymorphisms in ICAM-1 may be associated with IBD. [source]

Reevaluation of the interaction between HLA,DRB1 shared epitope alleles, PTPN22, and smoking in determining susceptibility to autoantibody-positive and autoantibody-negative rheumatoid arthritis in a large UK Caucasian population

ARTHRITIS & RHEUMATISM, Issue 9 2009
Ann W. Morgan
Objective To define interactions between the HLA,DRB1 shared epitope (SE), PTPN22, and smoking in cyclic citrullinated peptide (CCP) antibody, and rheumatoid factor (RF),positive and ,negative rheumatoid arthritis (RA). Methods Data on ,5,000 RA patients and ,3,700 healthy controls recruited from 6 centers in the UK were analyzed; not all centers had both genotype data and smoking data available for study. The magnitude of association was assessed in autoantibody-positive and -negative subgroups. The effect of smoking on antibody status among cases was assessed following adjustment for year of birth and center, using Mantel-Haenszel analysis. Analyses of the combined effects of PTPN22, HLA,DRB1 SE, and smoking were performed using additive and multiplicative models of interaction within a logistic regression framework. Results The combined effects of PTPN22, HLA,DRB1 SE, and smoking were defined, with no evidence of departure from a multiplicative model. Within the case population, all 3 factors were independently associated with the generation of CCP antibodies (odds ratio [OR] 11.1, P < 0.0001), whereas only HLA,DRB1 SE and smoking were independently associated with RF production (OR 4.4, P < 0.0001). There was some evidence of increasing likelihood of antibody positivity with heavier smoking. Finally, we demonstrated that smoking was associated with the generation of both CCP and RF antibodies (OR 1.7, P = 0.0001). Conclusion PTPN22 appears to be primarily associated with anticitrulline autoimmunity, whereas HLA,DRB1 SE is independently associated with RF. This study has confirmed associations of specific gene,environment combinations with a substantially increased risk of developing RA. Further work is needed to determine how these data can be used to inform clinical practice. [source]

Investigation of the MHC2TA gene, associated with rheumatoid arthritis in a Swedish population, in a UK rheumatoid arthritis cohort

ARTHRITIS & RHEUMATISM, Issue 11 2006
Stephen Eyre
Objective A recent study of rheumatoid arthritis (RA) showed an association with a functional single-nucleotide polymorphism (SNP) mapping to the promoter region of the MHC2TA gene on chromosome 16p13 in a Swedish population. Interestingly, evidence for linkage to this region has been detected previously in a subgroup of UK RA families carrying 2 copies of shared epitope (SE) alleles. Therefore, we undertook this study to investigate the association of the MHC2TA gene promoter with RA in a UK Caucasian population. Methods Association with 5 SNPs spanning the promoter region of the MHC2TA gene was investigated in 813 UK RA patients and 532 population controls. Association with a functional putative RA-causal polymorphism (,168*G/A [rs3087456]) was tested in a total of 1,401 UK RA patients and 2,475 controls. Genotyping was performed using a Sequenom MassArray platform. Estimated haplotype frequencies were generated using the expectation-maximization algorithm and compared between patients and controls. Results All SNPs were in Hardy-Weinberg equilibrium. No evidence for association was found, either with the putative RA-causal polymorphism (,168*G/A) or with the other SNPs tested. Haplotype analysis revealed extensive linkage disequilibrium across the promoter region but no evidence for association. Stratifying the data set by carriage of SE alleles did not alter the conclusions. Conclusion A functional polymorphism of the MHC2TA gene locus previously associated with RA in a European population has not been associated with RA in a UK population. These findings do not provide support for the notion that this gene plays a major role in the etiology of RA. [source]

Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progression

CLINICAL ENDOCRINOLOGY, Issue 1 2010
Kadija Yesmin
Summary Objective, Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region. Design, A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region. Patients, A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort. Measurements, We used the ,2 -test to investigate association between the Tag SNPs and GD. Results, Association between the rs1801274 (P,= 0·003, OR = 1·12 [95% CI = 1·03,1·22] and rs6427598 (P = 0·012, OR = 0·90 [95% CI = 0·83-0·98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes. Conclusions, This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general. [source]