Article

Understanding type 1 diabetes through genetics: advances and prospects

Departments of Pediatrics and Human Genetics, McGill University, Montreal, Québec, Canada H3H 1P3. Constantin.
Nature Reviews Genetics (Impact Factor: 39.79). 11/2011; 12(11):781-92. DOI: 10.1038/nrg3069
Source: PubMed

ABSTRACT Starting with early crucial discoveries of the role of the major histocompatibility complex, genetic studies have long had a role in understanding the biology of type 1 diabetes (T1D), which is one of the most heritable common diseases. Recent genome-wide association studies (GWASs) have given us a clearer picture of the allelic architecture of genetic susceptibility to T1D. Fine mapping and functional studies are gradually revealing the complex mechanisms whereby immune self-tolerance is lost, involving multiple aspects of adaptive immunity. The triggering of these events by dysregulation of the innate immune system has also been implicated by genetic evidence. Finally, genetic prediction of T1D risk is showing promise of use for preventive strategies.

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    • "DN is a common complication of type 1 and type 2 diabetes , which have been associated with very distinct disease risk loci [Figure 2 and reviewed in Ntzani and Kavvoura (2012), Polychronakos and Li (2011)]. Results of genetics studies are extensively discussed in two recent reviews (Gu and Brismar, 2012; Palmer and Freedman, 2012), we therefore will focus only on the genetic association of ELMO1, CNDP1, and FRDM3 loci with DN risk, as they were detected in both GWAS and candidate gene approach studies. "
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    Frontiers in Pharmacology 12/2013; 4:159. DOI:10.3389/fphar.2013.00159 · 3.80 Impact Factor
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    • "The main determinant of risk of developing CD is the HLA DQB1*02-DQA1*05 (HLA-DQ 2.5) haplotype and for T1DM both the HLA DRB1*03-DQB1*0201 and DRB1*04-DQB1*0302 (DR3-DQ2.5 and DR4-DQ8) haplotype [31] [32]. Our data confirm the high prevalence of HLA-DQ 2.5 haplotypes in patients with both T1DM and CD [7] [33]. "
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    • "The aforementioned T1D therapies are directed only at the consequences of the disease rather than the causative agent(s). While the ultimate cause of T1D is not currently defined and is likely multifactorial [5], T cells specific for islet antigens are the proximate cause of β cell destruction. Diabetogenic T cells that have been inappropriately activated and allowed to escape central and peripheral tolerance mechanisms (possibly due to assistance from aberrant innate cells [6]) have been implicated in β cell damage in both the nonobese diabetic (NOD) mouse and the human form of disease. "
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