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Two stars means the confidence level in the research is currently low. The website instructs me that “the condition (Gout) is caused by the accumulation of crystallized uric acid in the internal organs and joints – particularly in the big toe – which causes painful arthritic inflammation.”
23andMe looks at 3 SNPs in the SLC2A9 gene to determine my risk for developing Gout. If you have a certain mutation in these three SNPs, your odds increase by 1.3, 1.3, and 1.4 times (for each SNP). I have one mutation out of the three possible, so I only have “slightly higher odds”.
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The most interesting bit of knowledge I learned is the dietary factors that increase risk for Gout – high fat, alcohol and protein consumption are common for those who develop the disease. One fellow 23andMe customer shared that he was eating meat and drinking beer everyday for a year for his Adkins diet. He didn’t say if he lost weight, but did say his Gout was painful - and his diet has since changed. Another person commented that a study found a supplement of 500mg of vitamin C per day over 2 months reduced uric acid levels in the blood of 184 men.
The Gout. James Gillray, 1799. From the Philadelphia Museum of Art.
See You Next Year
Taking a two-week vacation for the holidays took a toll on the timeliness of this post. So let me wish everybody a belated Seasons Greetings, and an extra wish for that Happy New Year.
Perspective from a Certified Genetic Counselor
Gout and the Holidays
It is difficult to find time to write a blog submission in this season of merriment. Saturday evening is the church wine and cheese party; Sunday evening is the book club potluck; Monday is team breakfast, followed by small group lunch potluck, followed by a departmental dinner that evening. This is just the next three days! With the holiday season comes all the wonderful food. So you might think that we decided to talk about risk association and gout because of the known relationship between wonderful food and gout. It is a reasonable assumption. However, the truth is that while I was home over Thanksgiving I learned that more than one of my family members is reported to have had gout—including my mother! I made the mistake of musing aloud with Marc, “I wonder if the 23andme report addresses risk for gout?” upon which Marc, ever resourceful and ready to delegate [dump!], replied, “Yours, December 14th”.
Gout is famous for its appearance in royal families throughout many centuries. It is more recently that the general diet for people living in Western societies has “improved” to the point that gout is more common. Gout is a great example of the complexity of common adult onset disease. It is quite significantly impacted by familial factors. But genetic factors are NOT the whole picture. It is influenced by gender and age (more men develop gout than women and older age increases appearance especially in women post-menopause), obesity and metabolic syndrome increase the chance that gout may develop, and those with hypertension and cardiovascular disease more often are diagnosed with gout. Finally, specific dietary choices and life events may lead to gout symptoms. The challenge has been to identify the specific contributors that lead to gout in the hope that effective medications can be given to prevent the painful episodes and joint damage that result from uric acid deposition.
The work to elucidate the mechanisms, metabolism and mystery of gout has led to new understanding of pathways and inter-relatedness of human (mammal) systems biology. We are so very complex and elegantly balanced, physiologically speaking! The development of gout is, for the most part, dependent on the levels of uric acid floating around in the blood stream. People with gout either produce too much uric acid, or more commonly, their bodies have a problem in removing it. Uric acid is one of the inescapable products of the breakdown of food and processing of cells. The kidneys are responsible for the majority of the management of uric acid. This is a version of gout for dummies—please use your healthcare provider for a real discussion of gout!
Grant’s 23andme report indicates that he is at elevated risk for gout. The report lists identified markers in the SLC2A9 urate transporter which is formally known as the solute carrier family 2 member 9 and its function is to move uric acid and glucose/fructose. Common variants in SLC2A9 are associated with increased levels of uric acid and gout. Of the three markers assessed in his report, he had two which conveyed typical risk and one (rs737267 “GG”) which conveyed 1.3 times the odds of gout. Grant’s result is given two stars (out of 4?) in research confidence. This may be because so many other SNPs appear to affect uric acid levels. In a recent meta-analysis published in Public Library of Science Genetics, researchers evaluated 28,141 participants of European descent and identified 954 SNPs in 9 locations that had genome-wide significance with impact on serum uric acid levels. Certain SNPs lead to more pronounced effect in uric acid levels in women, while other SNPs elevate uric acid more strongly in men. The writers go on to suggest that it is the interplay between the SNPs, other proteins in the cellular environment and the uric acid levels in the blood that will contribute to whether one develops gout.
Gout and the Family
What about me and gout in my family? First of all, I do have two first degree relatives known to have gout. I recall that a brother had one experience with a really painful big toe that was labeled gout. I knew that my maternal uncle had to give up milking up cows because of arthritis in his knees—reported as osteoarthritis due to repeatedly kneeling to hook-up milking machines (pretty plausible). I knew that my grandfather had arthritis so bad that he sometimes had to crawl to the barn (no milking machines). I knew that my mother had a serious flare of non-rheumatoid arthritis in her feet, so bad that she could not keep the sheet resting on her toes. But I did not know that it was labeled gout and I haven’t even mentioned the family history of kidney stones. The brother above has had kidney stones that tested positive for uric acid. Now comes the “do I have…”, the episodes of curiously sharp pain in my big toe joint??? Was it just the choice of shoes????