What does ankylosing spondylitis trigger in some and not others?

Why does it effect us specifically?

The single biggest ‘penny drop’ moment for me was how our individual genetics, diet and environment are all deeply connected.

This is something Alan Ebringer references in his early papers on Ankylosing Spondylitis.

The idea is this…

There is a far higher incidence of ‘active’ ankylosing spondylitis developing in populations who are not genetically predisposed to the Western diet.

Or to put it another way (because the Western diet is a recent phenomenon) in populations where certain elements of the Western diet cannot be processed by individuals from certain populations.

I want to unpack everything as much as possible because this is a fascinating area.

When looking at this need to focus specifically on 3 things:

1. Which populations have the highest propensity for the gene most associated with ankylosing spondylitis, HLA-B27
2. What percentage of the people within these populations go on to develop ankylosing spondylitis
3. The diet and lifestyle of people within these populations (or their ancestors) prior to their exposure to the Western diet

Up to 90% of people with ankylosing spondylitis have the HLA-B27 gene

HLA-B27 is the gene most associated with ankylosing spondylitis.

Abhijeet Danve, MD, director of the spondyloarthritis program at Yale, puts the figure at around “80 to 90 percent of patients”. Others put it higher still.

But before we go any further it’s worth clarifying two very important points.

Not everyone with the HLA-B27 gene will develop ankylosing spondylitis. In fact only around 2% to 10% (source) go on to develop the disease.

Second, it is still absolutely possible to develop ankylosing spondylitis without having the HLA-B27 gene. It’s less common but it does happen. Some interesting findings were made in this Chinese study here.

For our purposes here, using this gene as a measure for individuals within populations who could have with the propensity to develop ankylosing spondylitis is an imperfect but effective tool.

We have results from a number of population studies where we can see the prevalence of this gene.

Let’s dive into the numbers.

North South divide: virtually no sub-Saharan Africans have the HLA-B27 gene compared to up to 50% of Yupik and Inuit populations

The findings are stark.

• In Sub-Saharan Africa the HLA-B27 gene is “virtually absent” (source)
• 2 – 6% of the population in the Mediterranean have the HLA-B27 gene
• 9.5% of the population in the UK have the HLA-B27 gene
• 14% – 16.6% of the population in Northern Scandinavia have the HLA-B27 gene (source)
• 25% – 50% of the population in the Arctic (Inuit, Yupik and Indigenous Northern American populations) have the HLA-B27 gene (source).

So we can see that the HLA-B27 gene is extremely prevalent in certain Northern, indigenous populations.

The existence of the HLA-B27 in these populations is not an anomaly.

The fact that in some Arctic regions as many as 50% of indigenous population have the HLA-B27 gene suggests there is something unique about the environment (the climate, food availability, disease prevalence and lifestyle).

This could mean a number of things…

1. As populations migrated there was some genetic advantage to having this gene (e.g. disease resistance, digestive ability)
2. There was no genetic disadvantage to not having this gene (pre the modern era Western diet/lifestyle)
3. There is something about the environment/diet/lifestyle in these northerly regions that prevents ankylosing spondylitis from ever developing.

Whole populations could not survive and thrive generation after generation for thousands of years with a crippling (when unmanaged) disease like ankylosing spondylitis.

Or to flip this on its head and put it another way.

There is something unique about ‘modern’ lifestyles in Western societies which triggers disease development.

This has been found with other diseases such as type 1 diabetes, psoriasis and irritable bowel syndrome.

Further reading:

Raised Incidence of Ankylosing Spondylitis Among Inuit Populations Could Be Due to High HLA‑B27 Association and Starch Consumption