Hl-a Antigens and Diabetes Mellitus

Nerup, Jørn; Platz, P.; Andersen, O. Ortved; Christy, M.; Lyngsøe, J.; Poulsen, Jacob E.; Ryder, Lars P.; Nielsen, Lillian Staub; Thomsen, Mögens; Svejgaard, A.

doi:10.1016/s0140-6736(74)91201-x

Cited by 721 publications

(305 citation statements)

References 18 publications

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“…In the 1970s, association and affected-sib pair linkage studies established the role of HLA genes in T1D predisposition (the HLA locus contribution to disease is referred to as IDDM1). [12][13][14] HLA studies also demonstrated that T1D and type 2 (non insulin-dependent) diabetes mellitus (T2D) were distinct disease entities, since T2D generally does not show an association with HLA, although certain subsets may demonstrate some association. 15 The variability in rates of T1D disease concordance in siblings who share two, one or zero parental HLA haplotypes in addition to the different concordance rates in monozygotic vs dizygotic twins, the risk in relatives, and the population prevalence implicates the existence of additional non-HLA genetic factors.…”

Section: Genetics Of T1dmentioning

confidence: 99%

Genetics of type 1 diabetes mellitus

2002

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Section: Genetics Of T1dmentioning

confidence: 99%

Genetics of type 1 diabetes mellitus

2002

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“…2 It is, therefore, perhaps not surprising to find that the human MHC class II gene region holds the largest number, and some of the longest recognized, associations with autoimmune diseases of any similar-sized region across the genome (Table 1). Early associations based on serological typing were established for multiple sclerosis, 3,4 type I diabetes 5,6 and celiac disease 7,8 which were subsequently resolved to specific human leukocyte antigen (HLA)-DR/DQ haplotypes. 9,10 Moreover, recent genomewide association studies using common single nucleotide polymorphism (SNP) markers have served to underline the remarkable contribution of this region in susceptibility to autoimmune disease, 11 which dwarfs any other genetic effect.…”

Section: Introductionmentioning

confidence: 99%

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

et al. 2009

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Major histocompatibility complex (MHC) class II molecules are central to adaptive immune responses and maintenance of selftolerance. Since the early 1970s, the MHC class II region at chromosome 6p21 has been shown to be associated with a remarkable number of autoimmune, inflammatory and infectious diseases. Given that a full explanation for most MHC class II disease associations has not been reached through analysis of structural variation alone, in this review we examine the role of genetic variation in modulating gene expression. We describe the intricate architecture of the MHC class II regulatory system, indicating how its unique characteristics may relate to observed associations with disease. There is evidence that haplotypespecific variation involving proximal promoter sequences can alter the level of gene expression, potentially modifying the emergence and expression of key phenotypic traits. Although much emphasis has been placed on cis-regulatory elements, we also examine the role of more distant enhancer elements together with the evidence of dynamic inter-and intra-chromosomal interactions and epigenetic processes. The role of genetic variation in such mechanisms may hold profound implications for susceptibility to common disease.

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“…An alternative to linkage studies is direct investigation of candidate genes or single-nucleotide polymorphisms (SNPs) for allelic association with T1D in either a case-control or family-based design. While many of these studies, particularly when performed in a case-control format, have suffered from poor reproducibility, they have resulted in the identification and characterization of several well-accepted T1D susceptibility loci such as the HLA region on chromosome 6p, 10 the insulin gene region on chromosome 11p, 11 and the CTLA4 gene region on chromosome 2q. 12,13 Furthermore, given the autoimmune etiology of T1D, it is not surprising that these identified loci and many of the candidate genes studied are predicted to have effects on the specificity or activation of the immune response.…”

Section: Introductionmentioning

confidence: 99%

A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families

et al. 2004

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Type I diabetes (T1D) is a complex disorder, which arises from the autoimmune destruction of the insulin-secreting b cells of the pancreas leading to a life-long dependence on exogenous insulin. A recent study of T1D cases and controls provided evidence for association between an allele of a functional single-nucleotide polymorphism (SNP) in the PTPN22 gene and T1D. In the current study, this SNP was genotyped in a collection of 406 multiplex T1D families. Significant evidence of the combined presence of association and linkage to T1D was obtained (P ¼ 2.5 Â 10 À5 ). Linkage studies in subsets of families defined by PTPN22 SNP genotypes suggest possible interaction with loci on chromosomes 3 and 21. Previous genome scans in this collection of T1D families, and others, have not yielded significant evidence of linkage in the region of the PTPN22 locus. However, the highly significant evidence of allelic association suggests that variation at, or near, this functional SNP contributes to the risk of T1D.

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Hl-a Antigens and Diabetes Mellitus

Cited by 721 publications

References 18 publications

Genetics of type 1 diabetes mellitus

Genetics of type 1 diabetes mellitus

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families

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