Novel Gene Associations in Type 1 Diabetes

Abstract

Recent genome-wide association studies have been able to identify multiple new gene loci affecting type 1 diabetes susceptibility, but the impact of these new defined loci seems to decrease in parallel with their number. The HLA gene region remains the main nominator of genetic susceptibility, although the identity of important genes and especially the mechanisms of their action are still largely unclear. Products of HLA and most other known risk genes are involved in regulation of the immune system in accordance with the autoimmune nature of the disease. The multitude of genes involved in the pathogenesis implies complex pathways where multiple steps in each may be essential in turning the balance of immune response to beta-cell destructing autoimmunity.

Risk genes and autoantibodies in Egyptian children with type 1 diabetes – low frequency of autoantibodies in carriers of the HLA‐DRB1*04:05‐DQA1*03‐DQB1*02 risk haplotype

“…To estimate the strength of the HLA class II association in the prediction of disease risk, we classified genotypes according to the presence of susceptible, protective, and neutral haplotypes into six groups as described earlier and compared the findings with that observed in the Finnish population . The Egyptian patients were strongly concentrated to groups with combinations of risk‐associated haplotypes: 71 of 101 (70.3%) Egyptian children with T1D had this type of genotype compared with only 217 of 622 Finnish children (34.9%, p = 1.6E−11).…”

LADA and T1D in Estonian population — Two different genetic risk profiles

“…Interestingly, the proportion of high-risk HLA genotypes has decreased among patients diagnosed with T1D during recent decades compared with those diagnosed a few decades earlier (Gillespie et al, 2004;Hermann et al, 2003). This change is associated with a greatly increased disease incidence during the past decades and indicates that greater environmental pressure affects the penetrance of T1D in genotypes with lower HLA risk (Ilonen and Hermann, 2010).…”

Being born in Sweden increases the risk for type 1 diabetes – a study of migration of children to Sweden as a natural experiment

“…Twin studies have confirmed the importance of heritage with a concordance rate of up to 70% (6). At least 10 genes have been reported to be involved, the most dominant being the HLA‐class II presenting gene on the short arm of chromosome 6, where some haplotypes (DR/DQ) are considered high risk alleles (7,8).…”