Судлаачид 1-р хэлбэрийн чихрийн шижин өвчний цаана генетикийн хувьд ялгаатай хоёр дэд хэв шинж байж болзошгүйг тогтоожээ.
АНУ болон Их Британийн эрдэмтэд 1-р хэлбэрийн чихрийн шижинтэй 9,091 хүн болон 14,157 хяналтын бүлгийн оролцогчдыг хамруулсан геном даяарх судалгааг (GWAS) анх удаа явууллаа. Энэхүү судалгаагаар өвчтөнүүдийг HLA-DR3 ба HLA-DR4 гэсэн хоёр генетик галилотипээр (haplotype) ангилж, тэдгээрийн өвчний үүсэл, хөгжлийн механизмыг харьцуулсан байна.
Судалгааны үр дүнгээс үзэхэд, HLA-DR3 хэв шинж нь харшил болон үрэвсэлтэй холбоотой дархлааны эсүүд болох мастоцитуудтай (mast cells) илүү хамааралтай байжээ. Харин HLA-DR4 хэв шинжийн үед нойр булчирхайн бета эсийг шууд устгадаг Т эсүүд (T cells) голлох үүрэг гүйцэтгэдэг болохыг тогтоосон байна.
Эрдэмтдийн дүгнэснээр, эдгээр хоёр генетик хэв шинж нь өвчний үүсэл, биологийн механизмын хувьд эрс ялгаатай байж болзошгүй юм. Энэхүү ялгаа нь сэтгэцийн эмгэгүүдийн хоорондын ялгаатай дүйцэхүйц хэмжээний ялгаатай болохыг тэд онцолжээ.
Энэхүү шинэ нээлт нь 1-р хэлбэрийн чихрийн шижин өвчнийг эмчлэх болон урьдчилан сэргийлэхэд хувь хүний генетик онцлогт суурилсан, илүү нарийвчилсан арга барилыг хэрэгжүүлэх боломжийг нээж байна. Цаашид эмнэлзүйн туршилтуудад өвчтөнүүдийн генетик мэдээллийг харгалзан үзэх нь эмчилгээний үр дүнг сайжруулахад чухал ач холбогдолтой гэж судлаачид Diabetologia сэтгүүлд нийтэлсэн судалгаандаа тэмдэглэжээ.
Дэлгэрэнгүйг эх сурвалжаас харах
↓Эх сурвалжийг нээх ↓
Identifying distinctive types of conditions like diabetes is helpful in two ways.
It means treatments can be personalized more precisely to individuals, and gives researchers a better idea of how to make those treatments more effective going forward.
When it comes to type 1 diabetes, there are two genetic patterns called HLA-DR3 and HLA-DR4 that are associated with a higher risk of the disease. However, while the end result is the same (type 1 diabetes), the early signs differ between the two patterns.
To investigate further, researchers from the US and UK ran the first-ever genome-wide association study (GWAS) separating type 1 diabetes patients by these two genetic signatures (technically known as haplotypes).
The purpose of a GWAS is to find areas of DNA potentially linked to a disease, and there were enough genetic differences between HLA-DR3 and HLA-DR4 participants in a sample of 9,091 people with type 1 diabetes and 14,157 controls to suggest we may be looking at two distinct subtypes.
The results have been published in Diabetologia.
“Type 1 diabetes is a complex disease characterized by autoimmune destruction of beta cells, but the underlying etiology is not well understood,” write the researchers in their published paper.
“The timing of progression to clinical diabetes varies widely across individuals, ranging from very early in childhood to adult onset.”
While the HLA-DR3 and HLA-DR4 genetic profiles and early signs had hinted at two types of type 1 diabetes, the new findings point to different biological machinery and mechanisms being involved as well.
The HLA-DR3 results pointed towards immune cells called mast cells, linked to allergies and inflammation, which keep watch for potential infection and foreign invasion.
With the HLA-DR4 genetic pattern, the body’s T cells were more strongly implicated. These immune cells directly attack other cells when ordered to, and in the case of type 1 diabetes, are known to destroy the beta cells in the pancreas.
“This reveals that type 1 diabetes in a DR3 and DR4 background may represent heterogeneous sub-forms of type 1 diabetes at the genetic level,” write the researchers.
To add some perspective, the researchers say the genes driving type 1 diabetes in HLA-DR3 cases compared to HLA-DR4 cases are as distinct and separate as they are when comparing schizophrenia and bipolar disorder.
And that brings us back to what we mentioned at the start: if type 1 diabetes can develop through different biological pathways, then separating treatments and treatment targets might be a more effective approach.
“Given heterogeneity in genetic risk and disease mechanisms in non-DR3/DR4 type 1 diabetes, effective prevention of type 1 diabetes may require distinct therapies in this group as well,” write the researchers.
These results now need to be tested further, to see if type 1 diabetes needs classifying in more detail as a disease that can be caused by several overlapping sets of triggers rather than one single route.
Knowing someone’s genetic background could help in figuring out the best treatment for them.
Now that researchers know there might be a possible distinction in the build-up to type 1 diabetes, it can be taken into account in future studies. The results of clinical trials of diabetes drugs, for example, could be separated by HLA-DR3 and HLA-DR4 patients.
Another possibility for future research is to follow type 1 diabetes patients more closely over time, to see how the condition develops based on genetic profile and other factors, such as autoantibody development and environmental exposures.
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“The results of our study should have wide application to the design of future studies,” write the researchers.
“DR3 and DR4 status could be considered in continued genetic association studies and risk prediction models of type 1 diabetes, for example, to understand risk variant interactions with HLA background.”
The research has been published in Diabetologia.
This article was fact-checked by Peter Dockrill and edited by Peter Dockrill. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.
