Genetic causes of type 2 diabetes
Most cases of type 2 diabetes involved many genes contributing small amount to the overall condition.[1] As of 2011 more than 36 genes have been found that contribute to the risk of type 2 diabetes.[2] All of these genes together still only account for 10% of the total genetic component of the disease.[2]
There are a number of rare cases of diabetes that arise due to an abnormality in a single gene (known as
Polygenic
Genetic cause and mechanism of type 2 diabetes is largely unknown. However,
Most SNPs that increase the risk of diabetes reside in
One of the examples of gene regulation in non-ORF SNPs that influences susceptibility is the changes in nucleotide sequence in
Another example of faulty gene regulation that influence the susceptibility is the SNPs in promoter regions of the genes. Gene like APOM and APM1 increase the risk of type 2 diabetes when there are SNPs in their proximal promoter regions. Promoters are sequences of DNA that allows proteins such as transcription factors to bind for gene expression, and when the sequences are modified, the proteins no longer bind as effectively, resulting in depressed level of gene expression. APOM is partly responsible for producing pre beta-high-density lipoprotein and cholesterol,[14] and APM1 is responsible for regulating glucose level in blood and fatty acid.[15] Decreasing the level these gene products reduce the body's ability to handle glucose, which leads to the increased risk of diabetes.
Since 2019 large sequencing studies have started to identify rare coding variants associated with type 2 diabetes risk, including variants in PAM and
It is important to note that those discovered genes do not determine susceptibility to diabetes for all people or cases. As the risk of diabetes is combination of the gene regulations and the interplay between those gene products, certain genes may not pose a threat to increase the susceptibility. TCF7L2 is one of the well-studied genes for diabetes susceptibility in most populations. However, SNPs in TCF7L2 that would normally increase the risk of diabetes does not affect the susceptibility for Pima Indians. However, this gene is associated with regulating the BMI for Pima Indian population.[19]
Various hereditary conditions may feature diabetes, for example
While obesity is an independent risk factor for type 2 diabetes that may be linked to lifestyle, obesity is also a trait that may be strongly inherited.[21][22] Other research also shows that type 2 diabetes can cause obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance.[23]
However, environmental factors (almost certainly diet and weight) play a large part in the development of type 2 diabetes in addition to any genetic component. Genetic risk for type 2 diabetes changes as humans first began migrating around the world, implying a strong environmental component has affected the genetic-basis of type 2 diabetes.[24][25] This can be seen from the adoption of the type 2 diabetes epidemiological pattern in those who have moved to a different environment as compared to the same genetic pool who have not. Immigrants to Western developed countries, for instance, may be more prone to diabetes as compared to its lower incidence in their countries of origins.[26] Such developments can also be found in environments which have had a recent increase in social wealth, increasingly common throughout Asia.
See also
- Epigenetics of diabetes Type 2
References
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- ^ "Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young". National Diabetes Information Clearinghouse (NDIC). National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Archived from the original on 2008-07-04. Retrieved 2008-08-04.
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- ^ Corona, Erik. "Geneworld". World Wide Patterns of Genetic Risk for Disease. Stanford University. Retrieved 11 September 2013.
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- ^ Cotran, Kumar, Collins; Robbins Pathologic Basis of Disease, Saunders Sixth Edition, 1999; 913-926.