Researchers have juvenile myasthenia gravis (MG) to a specific variant, or allele, of the HLA gene among Norwegians.
Their study, “Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated with prepubertal onset,” appeared in the journal PLOS ONE.
The disease mechanism that causes MG is complex, as it involves both genetic and environmental factors. While MG is not necessarily inherited, there is significant co-occurrence of autoimmune diseases among families of MG patients. MG also occurs more frequently among identical twins than among fraternal twins, indicating the existence of a genetic component.
The human leukocyte antigen (HLA) system is a gene complex, which is a group of genes that code for individual components of a protein complex called the major histocompatibility complex (MHC) in humans. The MHCs are cell-surface proteins that help regulate the immune system, and many autoimmune diseases have been linked to altered MHC proteins.
Alleles refer to alternative forms of a gene. Each person has two alleles per gene, one inherited from the mother and one from the father. Patients of similar origins tend to have similar alleles compared to people of different backgrounds. In MG, certain alleles that code for HLA genes and are found in some populations appear to have a stronger correlation with the disease.
In MG patients of European origin, the HLA-B*08 allele is associated with early onset of MG. The strongest HLA allele that denotes a risk for late-onset MG is DRB1*15:01. While researchers have conducted multiple studies on genetic associations with adult MG, none have focused on juvenile MG, which develops at the age of 18 or younger.
This latest study aimed to determine the genetic risk factors in Norwegian juvenile MG patients by looking at the specific HLA alleles present in this population. It included 43 juvenile MG patients and 368 controls. To determine their genetics, researchers used a technique called next-generation sequencing in five HLA genes that are part of the complex. Results showed that a link between juvenile MG and the alleles HLA-B*08 and HLA-DRB1*04:04.
Researchers then divided this group into patients who had either postpubertal or prepubertal onset to see if there was a difference. They discovered that HLA-DRB1*04:04 was positively associated with a prepurbertal onset. The HLA-B*08 allele was most frequently observed in postpubertal onset MG (40.4 percent of the total) but was also increased among prepubertal onset MG (23.5 percent).
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