| 1. |
- Amundsen, S. S., et al.
(författare)
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Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 64:5, s. 593-9
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Tidskriftsartikel (refereegranskat)abstract
- In order to extend our previous findings of genetic linkage to the CD28/CTLA4/ICOS region on chromosome 2q33 (CELIAC3) in coeliac disease (CD), we have investigated 22 genetic markers in 325 Norwegian/Swedish multiplex and simplex CD families. We found both linkage and association with several markers, primarily in the multiplex material. We observed strong linkage disequilibrium (LD) between SNPs (Single Nucleotide Polymorphisms) within an LD block delimited by MH30 and D2S72. A haplotype of this region marked by the alleles -1147*T: + 49*A:CT60*G:CT61*A was significantly associated with CD, suggesting that one or more polymorphisms of this haplotype, possibly -1147*T, are involved in CD susceptibility. The CT60 SNP, a polymorphism found to be most strongly associated with some other immune-mediated diseases, was not associated with CD, as this SNP was part of both associated and non-associated haplotypes. Moreover, our results suggest that CELIAC3 harbours several independent loci contributing to CD susceptibility.
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| 2. |
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| 3. |
- Barbron, Marie-Claude, et al.
(författare)
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Meta and pooled analysis of European coeliac disease data
- 2003
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 11:11, s. 828-834
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Tidskriftsartikel (refereegranskat)abstract
- Four full genome scans have been carried out by the partners of the European cluster on coeliac disease as well as follow-up studies of candidate regions. No region outside HLA showed significant linkage to the disease in any single study. We first applied a meta-analysis based on a modification of Genome Screen Meta-Analysis to take into account the different linkage statistics, the arbitrariness of bin cutoff points, as well as the sample size of each study. We then performed a pooled linkage analysis of all families and raw genotypes. Besides the HLA region, already known to harbour a risk factor for coeliac disease, both approaches leave very little doubt on the presence of a genetic risk factor in the 5q31-33 region. This region was suggested by several individual studies, but did not reach statistical values high enough to be conclusive when data sets were analysed separately.
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| 4. |
- Gudjonsdottir, Audur, 1959, et al.
(författare)
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The risk of celiac disease in 107 families with at least two affected siblings.
- 2004
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Ingår i: Journal of pediatric gastroenterology and nutrition. - 0277-2116 .- 1536-4801. ; 38:3, s. 338-42
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Screening for celiac disease (CD) in the apparently healthy members of 107 nuclear families with two affected siblings (sib pair) and estimating the risk of CD in siblings and parents. METHODS: One hundred seven families from Sweden and southern Norway with at least two affected children were investigated. Frozen sera from 187 of the 192 healthy parents and from 94 of 95 siblings without diagnosed CD were examined for total immunoglobulin A (IgA) and anti-endomysial antibodies (EMA). Individuals with positive antibody titers underwent small intestinal biopsy. RESULTS: Positive test for EMA was found in 6 of 94 (6.3%) siblings without previously diagnosed CD and in 8 of 189 (4.2%) parents. CD was confirmed by small intestinal biopsy in all siblings and seven parents. The estimated risk for CD in multiply affected families was 26.3% for siblings and 12.9% for parents. An unexpected male preponderance was found among the new CD cases (10 males, 3 females). CONCLUSION: The risk of CD in the members of nuclear families with two affected children is approximately three times higher than that when only one child is affected. The high male preponderance of new cases is unexpected and could not be explained fully by more silent disease in males as compared with females. Considering the high level of knowledge about CD in these families, the number of undiagnosed cases is surprisingly high. The authors suggest that serologic screening should be offered to all first-degree relatives of patients with CD.
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| 5. |
- Holopainen, Päivi, et al.
(författare)
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Candidate gene region 2q33 in European families with coeliac disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 63:3, s. 212-22
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome region 2q33 harbours a cluster of genes, CTLA-4, CD28, ICOS and closely located PD-1, all related to immune activation and considered as promising candidate genes for susceptibility to coeliac disease (CD). We present here the results of a genetic linkage and association analysis of nine markers located in this gene region in a large combined European material of 796 families with CD from Finland, Sweden, Norway, UK, France and Italy. The joint analysis supports earlier findings that this susceptibility locus, assigned as CELIAC3, merits further studies. Nominally significant linkage to CD was found in 314 families including affected sib pairs. Each of the five populations showed weak associations to several marker alleles, but the analysis revealed, however, no conclusive evidence for a primary functional gene or gene variant present in the total set of families. The results suggest that the CD risk due to 2q33 gene region is complex and may involve more than one susceptibility allele, which possibly differ from other autoimmune diseases.
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| 6. |
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| 7. |
- Kullberg-Lindh, Carola, 1959, et al.
(författare)
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Quantitative analysis of CMV DNA in children the first year after liver transplantation.
- 2003
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Ingår i: Pediatric transplantation. - 1397-3142. ; 7:4, s. 296-301
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Tidskriftsartikel (refereegranskat)abstract
- CMV infection is a major problem after solid organ transplantation especially in children where primary infection is more common than in adults. Early diagnosis is critical and might be facilitated by quantitative analysis of CMV DNA in blood. In this retrospective study of 18 children who had a liver transplantation 1995-2000, serum samples were analysed by Cobas Amplicor Monitor (Roche). Four patients developed symptomatic CMV infection at a mean time of 4 wk after transplantation. They showed maximum CMV DNA levels in serum of 26 400, 1900, 1300 and 970 copies/mL, respectively. In comparison, CA Monitor was positive, at a low level (415 copies/mL), in one of 11 patients with asymptomatic (4) or latent (7) infection. CMV IgM was detected at significant levels (> or =1/80) in all four patients with symptomatic, and in one with asymptomatic CMV infection. Eight patients were given one or several courses of ganciclovir. Five of these lacked symptoms of CMV disease, and had low (415 copies/mL) or undetectable CMV DNA in serum. The data suggest that quantitative analysis of CMV DNA may be of value in early identification of CMV disease and for avoiding unnecessary antiviral treatment.
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| 8. |
- Louka, A S, et al.
(författare)
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HLA in coeliac disease families: a novel test of risk modification by the 'other' haplotype when at least one DQA1*05-DQB1*02 haplotype is carried.
- 2002
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Ingår i: Tissue antigens. - 0001-2815 .- 1399-0039. ; 60:2, s. 147-54
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Tidskriftsartikel (refereegranskat)abstract
- Predisposition to coeliac disease (CD) involves HLA genes. We investigated whether any haplotypes modify risk when carried trans to a known high-risk haplotype, DQA1*05-DQB1*02. Earlier attempts to rank levels of risk contributed by the 'other' haplotype were burdened by use of case-control populations; haplotype frequencies were estimated and homozygosity was only presumed. In contrast, exact haplotypes can be determined and allele transmission can be traced in families. A similar study in narcolepsy reported strata of different degrees of predisposition, attributable to the 'other' haplotype. A gene dosage effect similar to that described for DQB1*02 in CD, has also been reported in narcolepsy. We genotyped 439 simplex/multiplex trios for DQA1 and DQB1. We designed a new statistic to test risk modulation by the trans haplotype, even if the affected offspring was homozygous. We tested for significant deviation in transmission of the 'other' haplotype, i.e., modification of DQA1*05-DQB1*02 risk. We also addressed the proposed difference in risk, between DQA1*05-DQB1*02 homozygotes and DQA1*05-DQB1*02/DQA1*0201-DQB1*02 heterozygotes, reported in Southern Europe. We confirmed a DQB1*02 gene dosage effect. However, no haplotypes were found to modify risk when carried trans to DQA1*05-DQB1*02, except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02 which were already known. We did not find credible evidence for a difference in risk conferred by DQA1*05-DQB1*02 and DQA1*0201-DQB1*02, when carried with DQA1*05-DQB1*02. The new test, which directly inspects haplotype transmissions rather than estimated haplotype frequencies, was used to demonstrate that the 'other' haplotype (except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02) does not modify risk conferred by DQA1*05-DQB1*02. The test is applicable to other diseases.
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| 9. |
- Louka, A S, et al.
(författare)
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The IL12B gene does not confer susceptibility to coeliac disease.
- 2002
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Ingår i: Tissue antigens. - 0001-2815. ; 59:1, s. 70-2
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Tidskriftsartikel (refereegranskat)abstract
- Coeliac disease (CD) is a chronic inflammatory disorder where dietary gluten is not tolerated. In the lesion there are gluten reactive T cells predominantly secreting gamma-interferon. Both HLA and non-HLA genes contribute to CD susceptibility. Interleukin-12 (IL-12) regulates gamma-interferon production. The IL12B gene is located in a region (5q31.1-33.1) where there is evidence for linkage with CD. Allele 1 of an IL12B 3'UTR single-nucleotide polymorphism leads to increased expression of IL-12, and was recently implicated in susceptibility for type 1 diabetes (T1D). We found no evidence for association of allele 1 to CD by the transmission/disequilibrium test or case-control approach. No increased frequency was observed in patients belonging to families where the disease was linked to markers on chromosome 5q. Unlike T1D, allele 1 does not appear to confer susceptibility to CD.
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| 10. |
- Margaritte-Jeannin, P, et al.
(författare)
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HLA-DQ relative risks for coeliac disease in European populations: a study of the European Genetics Cluster on Coeliac Disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 63:6, s. 562-7
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Tidskriftsartikel (refereegranskat)abstract
- Coeliac disease is an enteropathy due to an intolerance to gluten. The association between HLA-DQ genes and CD is well established. The majority of patients carry the HLA-DQ heterodimer encoded by DQA1*05/DQB1*02, either in cis or in trans. The remaining patients carry either part of the DQ heterodimer or DQA1*03-DQB1*0302. The aim of the study was to estimate the risks associated with different DQ genotypes in European populations. HLA information was available for 470 trio families from four countries: France (117), Italy (128), and Norway and Sweden (225). Five DQA1-DQB1 haplotypes were considered and control haplotype frequencies were estimated from the set of parental haplotypes not transmitted to the affected child. The possible genotypes were grouped into five genotype groups, based on the hierarchy of risk reported in the literature. A north-south gradient in the genotype group frequencies is observed in probands: homogeneity is strongly rejected between all country pairs. For each country, the relative risks associated with each genotype group were computed taking into account the control haplotype frequencies. Homogeneity of relative risks between countries was tested pairwise by maximum likelihood ratio statistics. The hypothesis of homogeneity of relative risks is rejected (P is approximately 10(-6)) for all country pairs. In conclusion, the gradient in the genotype group frequencies in probands is not only due to differences in haplotype frequencies but also due to differences in genotype relative risks in the studied populations; the relative risks associated with each DQ genotype group are different between northern and southern European countries; neither are they ordered in the same way.
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