Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3)

Dechairo, Bryan; Dimon, Claire; Heel, David A. van; Mackay, Ian; Edwards, Matthew; Scambler, Peter J.; Jewell, D P; Cardon, Lon R.; Lench, Nicholas; Carey, Alisoun H.

doi:10.1038/sj.ejhg.5200687

Cited by 68 publications

(33 citation statements)

References 46 publications

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“…The human leucocyte antigen (HLA) complex is located on the IBD3 locus (Williams et al, 2002;van Heel et al, 2004). HLA class II variants are associated with the susceptibility and phenotype in both CD and UC (Satsangi et al, 1996;Hampe et al, 1999;Stokkers et al, 1999;Yang et al, 1999;Dechairo et al, 2001). We previously reported on the exon 4 variation of the Tim-1 gene, and the polymorphisms of eotaxin-2 and eotaxin-3 are associated with UC in the Korean population Park et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Identification of the polymorphisms in IFITM3 gene and their association in a Korean population with ulcerative colitis

Seo

Lee

et al. 2010

Exp Mol Med

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Interferons play critical roles in tumor pathogenesis by controlling apoptosis and through cellular anti-proliferative and differentiation activities. Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFN and cellular anti-proliferative activities. Expression levels of IFITM genes have been found to be up-regulated in gastric cancer cells and colorectal tumors. IFITM3 (also known as 1-8U) is a member of the IFITM family, and has been described as a key player in specification of germ cell fate. IFITM3 was first isolated from a genetic screen aimed at identifying genes involved in acquisition of germ cell competence. It has been proposed that epiblast cells have the highest expression of IFITM3 initiated germ cell specification and that homotypic association can discriminate germ cells from their somatic neighbors. In an attempt to better understand the genetic influences of IFITM3 on ulcerative colitis, we have identified possible variation sites and single nucleotide polymorphisms (SNPs) through two exons and their boundary IFITM3 intron sequences including the ∼2.1 kb promoter regions. To determine whether or not these IFITM3 SNPs are associated with susceptibility to ulcerative colitis, frequencies of the genotype and allele of IFITM3 polymorphisms were analyzed on genomic DNAs isolated from patients with ulcerative colitis and from healthy controls. We also investigated the haplotype frequencies constructed by these SNPs in both groups. In this study, we also showed that expression level of IFITM3 mRNA was significantly higher in tissues of the ileum and cecum of the digestive system. We identified a total of seven SNPs and multiple variation regions in the IFITM3 gene. The genotype frequency of the g.-204T＞G polymorphism in patients with ulcerative colitis was significantly different from that of the control group. Our results strongly suggest that polymorphisms of the IFITM3 gene may be associated with susceptibility to ulcerative colitis.

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Section: Discussionmentioning

confidence: 99%

Identification of the polymorphisms in IFITM3 gene and their association in a Korean population with ulcerative colitis

Seo

Lee

et al. 2010

Exp Mol Med

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“…Genotyping has been performed using the ABI MD10 (Applied Biosystems, Warrington, UK) set of microsatellite markers for genome-wide screening. 15 Ethics committee approval was obtained and all participants gave written informed consent. Families were recruited in four European countries, namely Germany, Italy, Sweden and UK.…”

Section: Methodsmentioning

confidence: 99%

Multiple QTL influence the serum Lp(a) concentration: a genome-wide linkage screen in the PROCARDIS study

et al. 2006

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The serum concentration of lipoprotein Lp (a) is known to be highly heritable and associated with cardiovascular risk. A genome-wide variance component linkage analysis was performed to localise quantitative trait loci (QTLs) influencing Lp(a) levels in a large cohort collected in the PROCARDIS coronary heart disease study. Highly significant linkage was detected at the previously described LP(a) locus on chromosome 6q27 (LOD 108). Taking into account the effect of the locus detected on chromosome 6, a highly significant LOD score was detected on chromosome 13q22-31 (LOD 7.0). Another significant region of linkage was observed on chromosomes 11p14 -15 (LOD 3.5).The significant peak at 13q22-31 shows an essential overlap with a locus modulating cholesterol in familial hypercholesterolemia. If the gene underlying these loci is the same, it will be a promising candidate target for manipulating LDLcholesterol and Lp(a). We also detected linkage at a previously identified locus influencing Lp(a) on chromosome 1q23 (LOD 1.5). Our findings provide new and confirmatory information about genomic regions involved in the quantitative variation of Lp(a) and serve as a basis for further studies of candidate genes in these regions.

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“…DNA was extracted from a 9-ml EDTA-anticoagulated sample of frozen whole blood using a standard technique. Genotyping has been performed using the ABI MD10 (Applied Biosystems, Warrington UK) set of microsatellite markers for genome-wide screening [9] . Ethics committee approval was obtained and all participants gave written informed consent.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Trait Genetic Linkage Analysis of Body Mass Index in Familial Coronary Artery Disease

et al. 2008

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Objective: Body mass index (BMI) is one of the most reproducible and commonly used proxies for obesity and is known to be influenced by many environmental causes as well as genetic factors. Identification of susceptibility genes for BMI regulation has been difficult. Reasons for these inconclusive results are both methodological and related to obesity aetiology. A genome-wide linkage analysis was performed to localise Quantitative trait loci influencing BMI in a large cohort collected in the PROCARDIS coronary heart disease study consisting of 1,812 informative families. Methods: Multipoint linkage analysis for BMI was conducted using both a variance component approach and a model-free regression method, and the resulting LOD scores were compared. Results: The strongest evidence for linkage was detected on chromosomes 13 (LOD 1.6). Other regions showing a LOD score greater than 1 were observed on chromosomes 3, 5, 11, 12 and 15. These results were mainly confirmed by the three different approaches used in the analysis. Conclusion: Our study did not find any locus with strongly supporting evidence for linkage to BMI even in such a large sample. Our results confirm the substantial genetic heterogeneity influencing BMI regulation that has emerged from the majority of genome scans so far published.

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Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3)

Cited by 68 publications

References 46 publications

Identification of the polymorphisms in IFITM3 gene and their association in a Korean population with ulcerative colitis

Identification of the polymorphisms in IFITM3 gene and their association in a Korean population with ulcerative colitis

Multiple QTL influence the serum Lp(a) concentration: a genome-wide linkage screen in the PROCARDIS study

Quantitative Trait Genetic Linkage Analysis of Body Mass Index in Familial Coronary Artery Disease

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