Hyperuricemia is the underlying cause of gout. This can occur for a number of reasons, including diet, genetic predisposition, or underexcretion of urate, the salts of uric acid. Renal underexcretion of uric acid is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%. About 10% of people with hyperuricemia develop gout at some point in their lifetimes. The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530 ?mol/l (7 and 8.9 mg/dl), the risk is 0.5% per year, while in those with a level greater than 535 ?mol/l (9 mg/dL), the risk is 4.5% per year.
Lifestyle Dietary causes account for about 12% of gout, and include a strong association with the consumption of alcohol, fructose-sweetened drinks, meat, and seafood. Other triggers include physical trauma and surgery. Recent studies have found dietary factors once believed associated are, in fact, not, including the intake of purine-rich vegetables (e.g., beans, peas, lentils, and spinach) and total protein. The consumption of coffee, vitamin C and dairy products, as well as physical fitness, appear to decrease the risk. This is believed partly due to their effect in reducing insulin resistance.
Genetics The occurrence of gout is partly genetic, contributing to about 60% of variability in uric acid level. Three genes called SLC2A9, SLC22A12 and ABCG2 have been found to commonly be associated with gout, and variations in them can approximately double the risk. Loss of function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia by reducing urate absorption and unopposed urate secretion. A few rare genetic disorders, including familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase superactivity, and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan syndrome, are complicated by gout.
Medical conditions Gout frequently occurs in combination with other medical problems. Metabolic syndrome, a combination of abdominal obesity, hypertension, insulin resistance and abnormal lipid levels, occurs in nearly 75% of cases. Other conditions commonly complicated by gout include: polycythemia, lead poisoning, renal failure, hemolytic anemia, psoriasis, and solid organ transplants. A body mass index greater than or equal to 35 increases a male's risk of gout threefold. Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function. Lesch-Nyhan syndrome is often associated with gouty arthritis.
Medication Diuretics have been associated with attacks of gout. However, a low dose of hydrochlorothiazide does not seem to increase the risk. Other medicines that have be en associated include niacin and aspirin (acetylsalicylic acid). The immunosuppressive drugs ciclosporin and tacrolimus are also associated with gout, the former particularly when used in combination with hydrochlorothiazide.