Are You Destined For Arthritis? A Review of Ryder et al

A QUESTION

 

My last post covered the modifiable risk factors for osteoarthritis. My conclusion based on the available evidence was that your best bet to reduce risk of osteoarthritis is to avoid joint injuries, don’t get too heavy and pick a job that doesn’t require a lifetime of heavy lifting, kneeling, squatting, stairs or working in cramped environments.

 

But what about the genetic component? Do we know if genetics play a role in the development and progression of osteoarthritis? If so, do we know what specific genes are the culprits?

 

SOME DATA

 

The Questions Restated

I found two large scale systematic reviews on genetics and arthritis that address the two questions I asked: 1) What percentage of osteoarthritis risk is heritable? 2) what are the specific genes that cause arthritis?

 

Heritability

Do genes determine whether or not you will get arthritis? The answer to this question is found in studies of twins. If identical twins are raised in different environments but both end up with the same rates of osteoarthritis then osteoarthritis would be considered a highly heritable trait.

 

In 2008 an article published in Rheumatology concluded that the heritability of osteoarthritis of the smallest finger joints x was 71% (distal interphalangeal), the larger finger joint 37% (proximal interphalangeal) and the wrist joints 14% (carpometacarpal). They found no such “genetic phenotype” for the hip and knee with a heritability of 1% for these joints Their analysis was based on examination of x-rays in the medical records of 992 identical and fraternal twins in the TwinsUK registry. The found no evidence of a genotype which is likely to get osteoarthritis everywhere [1].

 

The short answer is: Yes for the fingers, no for the hips and knees.

 

Specific Genes

Finding specific genes that are linked to arthritis would 1) allow one to find out one’s risk of arthritis from genetic testing and 2) Direct the development of treatments specific to these genetic causes.

 

Specific Genes by Type

 

Suspect 1: Genes that Affect Inflammation

In 2011 a systemic review published in Osteoarthritis and Cartilage by H.J.M Kirkhof et al, found that the variations in the gene for the inflammatory mediator interleukin-1 beta did not have an association with hip or knee osteoarthritis but that the gene for interleukin-1 receptor antagonist might have a role in severity[2].

 

Suspect 2: Estrogen

There are many genes which play a role in osteoarthritis, but only a few play such as Estrogen receptor alpha (ER-1) have a large enough role that they stand out. Estrogen related genes also have different effects on different genders [3].

 

Suspect 3: Growth and Development Genes

In 2009 an article was published in the journal of Arthritis and Rheumatism by a group lead by Evangelos Evangelou. Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand. They found that Growth and Development Factor 5 was a predictor of knee osteoarthritis across populations [4,5].

 

Suspect 4: Cartilage

Epigenetic effects are environmental impacts on genes that change what those genes end up doing. DNA damage such as methylation can effect the genes related to cartilage and this influence has been investigated in osteoarthritis [5].

 

Specific Genes by Body Region

A group of British researchers headed by JJ Ryder, published a systematic review on the state of research on specific genes related to joint arthritis and spinal degenerative disease. They found that many studies had been published which linked a single gene to arthritis but very few of these genes-arthritis links were verified by multiple studies. [5]

 

Hand Arthritis

-AGC1 (14,15,17) HFE (57,58)

Hip and Knee Arthritis

-ASPN (19-22),

Knee Only

-ESR1 (48,49), IL1A and IL1RN (67,68), PTGS2 (11,12)

Knee and Spine

-VDR (50,52,89-94)

The short answer is: We have some suspects but the data is preliminary. No test can tell you that you will certainly get osteoarthritis and I don’t see any magical cures on the near horizon.

 

CONCLUSION

 

This was a messy topic to research. There is no dirth of research on osteoarthritis but I often found conflicting information. Genes related to cartilage, growth and development, estrogen and inflammation all play a role in the development and progression of osteoarthritis. Many of the gene-arthritis associations are preliminary and are awaiting a second study to validate the association. Heritability plays a role with the hands and knees seeming to be the most heritable.

 

These results aren’t particularly empowering, but on the flips side, genetics aren’t everything. Preventative measures focused at reducing joint injury, body weight and repetitive overuse can reduce the risk of osteoarthritis. And treatments such as joint mobilization, gait modifications, strengthening and medications targeting inflammation can reduce the symptoms and slow the progression of the disease.

 

REFERENCES

 

1 MacGregor, A.J. 2008 The genetic influence on radiographic osteoarthritis is site specific at the hand, hip and knee. Abstract here: http://rheumatology.oxfordjournals.org/content/48/3/277.long

2 Kerkhof 2011. Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis. Abstract here: http://www.sciencedirect.com/science/article/pii/S1063458410004000

 

3. Riancho 2010- Common variations in estrogen-related genes are associated with severe large-joint osteoarthritis: a multicenter genetic and functional study. Osteoarthritis Cartilage. 2010 Jul;18(7):927-33. doi: 10.1016/j.joca.2010.04.002. Epub 2010 Apr 22. Abstract here: http://www.ncbi.nlm.nih.gov/pubmed/20417295

4. Evangelou 2009 Arthritis Rheum. 2009 Jun;60(6):1710-21. doi: 10.1002/art.24524.Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand. http://www.ncbi.nlm.nih.gov/pubmed/19479880

 

5. Reynard 2012: Genetics and epigenetics of osteoarthritis. Mar;71(3):200-4. doi: 10.1016/j.maturitas.2011.12.001. Epub 2011 Dec 29. Abstract here: http://www.ncbi.nlm.nih.gov/pubmed/22209350

 

6. Ryder 2007- Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review. Ann Rheum Dis. 2008 May;67(5):584-91. Epub 2007 Aug 24. Abstract here: http://www.ncbi.nlm.nih.gov/pubmed/17720722

 

20131202-080824.jpg

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s