Gout: it strikes suddenly, it really REALLY hurts, and you can blame your ABCG2 gene.
By Dona Suri
Inflamed, swollen big toe – excruciatingly painful. Diagnosis: GOUT ! Actually, any of the joints can be afflicted … ankles, elbows, hands, wrist … anywhere.
No mystery about the identity of the mischief-maker: it’s uric acid. In addition to gout, uric acid is responsible for gastric disturbances and kidney stones.
Gout strikes overnight. In fact, it’s common for people to wake up in the middle of the night with severe pain. The first 24 hours are the worst. Left untreated, gout will eventually subside in maybe two weeks. But toughing it out is not a wise thing to do: gout can spread to other joints in the body and lead to worse conditions.
If you are one of those people who just likes to suffer … psychiatrists have a name for that condition and you should be getting treatment for that too. Normal people do not suffer when medication is available.
If you have gout, you are not alone. About one in 25 Americans are with you – that’s around 8.3 million people. About three-fourths of them are men and the rest are postmenopausal women. (Estrogen wards off gout.) Gout has become more prevalent too … the incidence rate has more than doubled since the 1980s.
Since gout is much more likely to afflict older people, the rise in incidence can be partially attributed to demographics: the Boomers are now past age 65 and even the Gen-Xers are on the verge of retirement. Some part of the blame falls to America’s obesity epidemic. Also, diuretics (water pills) commonly used to bring down high blood pressure can have gout as a side effect.
What really predisposes is genetics. If your grandpa suffered from gout, you are likely to suffer too. Residing in your kidneys you have a gene called ABCG2; it commands the process of filtering urate out of your blood and discharging it into your urine. Any change in the ABCG2 gene impairs urate removal. Excess urate turns into minute crystals that accumulate in one or more joints. When this happens, your immune system cells rush in screaming. Result: inflammation, swelling and pain. Researchers note that a mutated ABCG2 gene is not solely responsible for the trouble. Dietary and environmental factors are also involved.
A 2018 researchers studied some 17,000 men and women. They took the genetic profile of each person, monitored what each person ate and analyzed blood urate levels. The goal was to predict who would develop gout.
Here’s what they found out about food –>
However, they also discovered that these foods accounted for less than 1 percent of the variation in blood levels of urate. Genetic factors, in comparison, were responsible for 23.9 percent of the variation.
The researchers concluded: “Genetic factors have a larger influence on serum urate than dietary factors. What surprised us was the magnitude of this difference, an almost 100-fold increase. In contrast with genetic contributions, diet explains very little variation in serum urate levels in the general population. Gout is genetic.”
Before we try to explain the malfunction underlying uric acid build-up, let’s see how things work when your ABCG2 gene is in good nick and you are not overweight or tucking in to too many “dangerous” foods.
It all starts with purine. A purine molecule can belong to the adenine family or the guanine family. Both families are molecules with nine atoms, four of which are nitrogen and the atoms are arranged in a double ring. The words adenine and guanine look vaguely familiar? Each of your DNA bits is an arrangement of Adenine, Guanine, Thymine and Cytosine. Besides being building blocks for DNA and RNA, purines provide energy and ensure cell survival and proliferation.
A small amount of our purine is made “in-house”: dead, dying or damaged cells degrade their nucleic acids, adenine and guanine, into uric acid. This purine is referred to as endogamous (growing or originating from within).
The bulk of our purine is contained in what we eat; it’s exogenous (growing or originating from outside). Most of this purine is derived from animal proteins.
Endogenous or exogenous, the purines wind up in the liver (and intestines, muscles, kidneys and vascular endothelium). Purines are transformed first into hypoxanthine and then into xanthine and finally into uric acid.
The process goes wrong if …
- our protein intake is high and more uric acid is produced,
- due to any one of the many reasons, one of which may be genetic, more uric acid is retained in the body.
Most gout cases are caused by the second malfunction. High uric acid levels in the blood cause monosodium urate crystals to form in the joints. Gout is a form of arthritis.
If a person has been suffering from gout for a long time, nodules of uric acid crystals may form around the joints. The nodules are called tophi.
The good news is that gout is the most easily treated form of arthritis.
Five drugs are available to treat severe and chronic gout: allopurinol, febuxostat, pegloticase, probenecid and colchicine. All of them work by preventing uric acid formation. Incidentally, caffeine may protect you from gout. In chemical structure, caffeine is very similar to allopurinol.
People who suffer an occasional gout flare-up usually need nothing stronger than naproxen and ibuprofen or some other over-the-counter, non-steroidal anti-inflammatory drug.
Chronic or occasional, an important part of the treatment is rest and a low protein diet with plenty of Vitamin C thrown in.
And wouldn’t you just know it … gout prevention (like everything else) demands watching your weight.
The Arthritis Foundation emphasizes the value of staying trim. Correct weight means reduced pressure on joints and a moderate, Mediterranean diet doesn’t cause high uric acid levels in the body. Plus, it’s good for heart health.
If you have had a bout of gout, the doctor is sure to advise you to get more exercise once the symptoms subside.
May you never, ever experience the pain of gout but if it strikes, head straight for your doctor. Do not just wait for it to go away by itself. If left untreated, gout increases the risk of other conditions, including cardiovascular disease and kidney stones.
