Polymyalgia Rheumatica (PMR) is a common inflammatory condition characterized by widespread aching and stiffness. This discomfort primarily affects the large muscle groups around the shoulders and hips, often presenting suddenly, with symptoms being most severe in the morning. PMR occurs almost exclusively in individuals over the age of 50. While the precise mechanism that triggers the inflammatory response remains unknown, researchers investigate both inherited and external factors that contribute to the disease’s onset.
Genetic Predisposition Versus Direct Inheritance
Polymyalgia Rheumatica is not a condition that is directly inherited like a simple Mendelian trait, where a single gene guarantees the disease’s development. Instead, the condition is considered to have a familial aggregation, meaning an individual can inherit an increased susceptibility, or genetic predisposition, that makes the immune system more reactive.
The statistical risk is evident in studies showing an elevated incidence among first-degree relatives of individuals with PMR, though the overall risk remains low. PMR is a multifactorial disease, requiring a combination of inherited susceptibility and external factors to manifest. This pattern of inheritance contrasts sharply with diseases caused by a single, dominant, or recessive gene.
Specific Genetic Markers Linked to Increased Risk
The inherited susceptibility to PMR is strongly linked to specific variations in genes that govern the immune system’s function. The most significant association has been found within the Human Leukocyte Antigen (HLA) system, which is a gene complex responsible for regulating immune response. These HLA genes produce proteins that help the immune system distinguish the body’s own cells from foreign invaders.
Particular alleles of the HLA-DRB1 gene, such as HLA-DRB1\04, are frequently observed in individuals diagnosed with PMR, especially in populations of Northern European descent. Researchers have specifically identified the HLA-DRB1\0401 and HLA-DRB1\0404 subtypes as conferring a notably increased risk. This genetic link suggests that the inherited tendency involves a specific immune system structure that may incorrectly initiate the inflammatory cascade characteristic of PMR.
Non-Genetic Factors That Increase Risk
Non-genetic factors play a significant role in determining who develops PMR. The disease is highly age-dependent, with the vast majority of cases occurring after age 50. Sex is also a factor, as women are approximately two to three times more likely to develop the condition than men.
A distinct geographic and ethnic pattern exists, showing a markedly higher prevalence in populations of Northern European or Scandinavian ancestry compared to those of Southern European, Asian, or African descent. The sudden onset of symptoms suggests an environmental trigger is involved. Researchers hypothesize that an infectious agent, such as a virus or bacterium, might act as this trigger, though no single definitive infectious cause has been conclusively identified.
The Gene-Environment Interaction Model of Causation
Polymyalgia Rheumatica is best explained by a gene-environment interaction model, where genetic susceptibility and external factors must converge for the disease to activate. An inherited genetic predisposition, such as the presence of high-risk HLA-DRB1 alleles, primes the individual’s immune system for an overreaction.
The trigger is believed to be an environmental factor, most likely an infection or other external stimulus, which initiates the autoimmune response in the genetically susceptible person. Neither the genetic factors alone nor the environmental exposure alone is sufficient to cause the condition. This complex interaction results in the dysregulated inflammatory response observed in PMR, leading to the characteristic muscle pain and stiffness.