The genetic factors that put us at risk to osteoarthritis are not completely understood.  However, there is one very common genetic condition that has been found to be involved in osteoarthritis.  This is a gene for a condition called hemochromatosis, which causes excessive iron to accumulate in the body.  Like iron causes rust on metals, it also causes damage to joints through a process called oxidative stress.

In one study of over 2,000 people, those with the gene mutations for hemochromatosis were far more likely to have arthritis of one or more joints, including the hands, hips, and knees.  According to the scientists, “The HFE [hemochromatosis] H63D variant may explain, at least in part, the prevalence of arthralgia [joint pain] in multiple joint sites and hand osteoarthritis in the general population.”

[Alizadeh, BZ, Njajou, OT, Hazes, JM. The H63D variant in the HFE gene predisposes to arthralgia, chondrocalcinosis, and osteoarthritis. Ann Rheum Dis 2007;66(11):1436-42.]

In a study of people with osteoarthritis of the ankle, doctors looked at the same gene mutations for hemochromatosis mentioned above.  Eleven of the 13 people studied had mutations of at least one hemochromatosis gene called H63D. According to the authors of this study, “A strong and statistically significant association was observed between HFE gene mutations and primary osteoarthritis in the ankle joint.”

[Carroll, GJ. Primary osteoarthritis in the ankle joint is associated with finger metacarpophalangeal osteoarthritis and the H63D mutation in the HFE gene: evidence for a hemochromatosis-like polyarticular osteoarthritis phenotype. J Clin Rheumatol 2006;12(3):109-13.]

The number of people who carry this gene is surprisingly high, being the most common genetic abnormality found in Caucasians of northern European descent.  It is thought that the first mutation arose some 70 generations ago in a single person of Celtic heritage in the British Isles. Today, it is estimated that one in 200 persons in the United States and Canada has both genes (Hfe C282Y and H63D) and one in 10 persons is a carrier (possessing one copy of the mutant allele). 

To put in further perspective, perhaps as many as 2 million Americans unknowingly have the double gene mutation, with another 35 to 45 million being silent "carriers" of the single gene mutation. If you are of Irish, English, Scottish, Norse, or Celtic heritage, you are potentially one of these people.  If you actually live in the British Isles, as many as 1 in 4 may be a carrier, with 1 in 64 carrying the double gene mutation.  In Australian whites, as many as 14 persons out of 100 is a carrier.

The first hint that you might have hemochromatosis would be elevated blood iron levels. However, hemochromatosis can occur without elevated blood iron.  If you have developed arthritis early in life (before age 40 or 50) you may wish to be tested for the hemochromatosis gene mutations.  If you have elevated blood iron levels, you may wish to talk to your doctor about having the following blood tests done:

Biochemical Tests for Iron Status

• Serum iron
• Serum ferritin
• Transferrin saturation
• Total iron binding capacity (TIBC)

Genetic Tests for Inherited Disease of Iron Accumulation

• Hfe mutation C282Y
• Hfe mutation H63D

If you are found to have hemochromatosis, it may be possible to improve your osteoarthritis by having regular blood draws.  Regular blood draws will gradually draw the excess iron from your system and lessen the effects of the damaging iron levels on your joint.  The only way to know if you have this condition, however, is to have the genetic profile done.

Another Genetic Link?

Doctors at the University of Munich, Germany, have recently looked at more than 4,000 genes from the cartilage of people with and without osteoarthritis.  These doctors wanted to see if certain genes were switched up or switched down (much like the dimmer switch in your dining room).  Several expected genes that deal with cartilage destruction were altered.  But one set of genes really stood out.  These were genes associated with oxidative stress or free radical injury.  Their names are superoxide dismutase and glutathione peroxidase.

Both genes were under-expressed, meaning their activity had been “dialed down.”  When these genes are shut down, the ability to defend against free radical injury is weakened. The doctors wrote that “This indicates that continuous oxidative stress to the cells and the matrix is one major underlying pathogenetic mechanism in OA.”

This research suggests the possibility that a diet or supplement regimen high in antioxidant vitamins and phytonutrients might be helpful in slowing cartilage destruction in OA.

[Aigner, T, Fundel, K, Saas, J, et al. Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. 2006;54(11):3533–3544.]