- Large genome-wide association study illuminates genetic risk factors for gout
- Hyperuricemia in Children and Adolescents: Present Knowledge and Future Directions
- 1. Introduction
- 2. Database
- 3. Reference Values of Uric Acid in Children and Adolescents
- 4.1. Gout
- 4.5.4. Chronic Kidney Disease (CKD)
- 5. Treatment of Hyperuricemia
- 5.1. Lifestyle Intervention
- 5.2. Xanthine Oxidase Inhibitors
- 5.3. Uric Acid Oxidase (Rasburicase)
- 6. Conclusion and Future Directions
- Conflicts of Interest
- Gout Caused by Genetics More Than Diet
- Common variants in the SLC28A2 gene are associated with serum uric acid level and hyperuricemia and gout in Han Chinese
- Genetics Drive Gout Risk Far More Than Diet
- What Role Does Diet Play in Gout Management?
- Become a Member
- Make a Honor or Memorial Gift
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- Genetics of serum urate concentrations and gout in a high-risk population, patients with chronic kidney disease
- Gout Risk Factor Less about Diet, More about Genes
Large genome-wide association study illuminates genetic risk factors for gout
Researchers, using a method called genome-wide association study, have illuminated the genetic underpinnings of high serum urate, the blood condition that brings on gout. The study, co-led by scientists at the Johns Hopkins Bloomberg School of Public Health, will inform efforts to develop screening tests for gout risk as well as potential new treatments.
The paper was published October 2 in Nature Genetics.
For their analysis, the researchers combined DNA and serum urate data from 457,690 individuals participating in 74 studies, and revealed 183 sites, or “loci,” in the genome where DNA variations are strongly associated with high urate levels. The vast majority of these loci had not been identified in prior studies.
The researchers mapped many of the loci to specific genes and found that a large proportion are active in liver and kidney cells, sites of urate generation and excretion, respectively.
They also showed that the 183 urate-associated loci could be used to predict gout risk in an independent group of more than 300,000 people.
“These findings may be useful in developing screening tests for gout risk so that patients who are at risk can adopt dietary changes to avoid developing the condition,” says study lead author Adrienne Tin, PhD, assistant scientist in the Department of Epidemiology at the Bloomberg School. “The urate-related gene variants and biological pathways uncovered here also should be useful in the search for new ways to treat gout.”
Gout affects more than 8 million people in the U.S. It occurs when urate (also called uric acid) becomes too concentrated in the blood and precipitates into solid crystals, most frequently in the joints.
The crystals trigger episodes of painful inflammation, especially in the big toes.
In the 16th century, gout plagued Henry VIII of England and many other historical figures, and was once known as the “disease of kings” because it occurred as a result of diets normally available only to the very wealthy.
Urate is a breakdown product of purine molecules, which are found much more in meat- or shellfish-heavy diets than in vegetarian diets. Alcoholic beverages, particularly beer, are also high in purine content. Gout has been increasing in prevalence around the world as many countries' diets have grown richer.
The meta-analysis by Tin and her colleagues included data from 288,649 people of European ancestry, 125,725 people of East Asian ancestry, 33,671 African Americans, 9,037 South Asians, and 608 Hispanics — 457,690 individuals in all. Of the 183 loci on the human genome where DNA variations are strongly linked to high serum urate levels, only 36 had been revealed in prior studies.
The team analyzed the 183 loci to come up with a genetic risk score for high serum urate. They then applied their risk scoring system to an independent sample of 334,880 people from a U.K.
medical research database, and found that the scoring accurately stratified them according to their chances of having gout. The prevalence of gout in the 3.
5 percent of people in the three highest risk score categories was more than triple that of people in the most common risk score category. This is similar to disease risks conferred by some classic, single-gene diseases.
To begin to understand the biological significance of the 183 loci, the researchers mapped these to known genes, and found that many of these genes normally are active in the kidneys, urinary tract, and liver — reflecting the important roles of the kidneys and liver in regulating serum urate levels. More detailed analyses revealed 114 specific urate-risk DNA variants, often in genes with known functions in urate processing in the kidneys and liver.
“These genetic variants we highlighted can now be studied further to identify how they contribute to high urate levels, and to determine whether they would be good targets for treating gout,” Tin says.
High bloodstream urate levels are known to correlate with high bloodstream levels of other important molecules including cholesterol, and the findings also illuminate a reason for this connection.
One of the apparent risk genes uncovered in the study, HNF4A, encodes a transcription factor that is known to regulate levels of cholesterol and triglycerides.
“We were able to confirm through cell-based experiments that this transcription factor also regulates an important urate transporter protein, ABCG2, in kidney cells,” Tin says.
Materials provided by Johns Hopkins University Bloomberg School of Public Health. Note: Content may be edited for style and length.
Hyperuricemia in Children and Adolescents: Present Knowledge and Future Directions
Recent evidence suggests that hyperuricemia is an important condition in children and adolescents, particularly in association with noncommunicable diseases. This review aims to summarize our current understanding of this condition in pediatric patients.
An analysis of serum uric acid reference values in a healthy population indicates that they increase gradually with age until adolescence, with differences between the sexes arising at about 12 years of age. This information should be taken into consideration when defining hyperuricemia in studies.
Gout is extremely rare in children and adolescents, and most patients with gout have an underlying disease. The major causes of hyperuricemia are chronic conditions, including Down syndrome, metabolic or genetic disease, and congenital heart disease, and acute conditions, including gastroenteritis, bronchial asthma (hypoxia), malignant disorders, and drug side effects.
The mechanisms underlying the associations between these diseases and hyperuricemia are discussed, together with recent genetic information. Obesity is a major cause of hyperuricemia in otherwise healthy children and adolescents.
Obesity is often accompanied by metabolic syndrome; hyperuricemia in obese children and adolescents is associated with the components of metabolic syndrome and noncommunicable diseases, including hypertension, insulin resistance, dyslipidemia, and chronic kidney disease. Finally, strategies for the treatment of hyperuricemia, including lifestyle intervention and drug administration, are presented.
Hyperuricemia is a laboratory abnormality often observed in children and adolescents. However, because of the low diagnostic value of serum uric acid (hereafter described as “uric acid”) alone, uric acid levels may not be adequately considered by pediatricians.
More attention has been drawn to hyperuricemia in children and adolescents by several recent studies reporting its association with obesity and noncommunicable diseases (NCDs), especially cardiovascular disorders. A search of the literature found only two reviews of hyperuricemia in children and adolescents [1, 2].
Although these reviews are comprehensive and well summarized, they have two major drawbacks. First, they do not adequately address the associations between hyperuricemia and NCDs. Second, recent findings of genetic studies on hyperuricemia are not fully discussed.
Therefore, this review aims to cover these topics and proposes future directions for research on hyperuricemia in children and adolescents.
Articles published from 2000 to 2018 were retrieved in searches of Medline and Web of Science. The search methodology consisted of both controlled vocabulary as in the National Library of Medicine MeSH and the keywords uric acid/hyperuricemia and child/adolescent. Reviews and case reports published before 2000 are included if considered to be of particular importance.
3. Reference Values of Uric Acid in Children and Adolescents
In adults, serum uric acid >7.0 mg/dL is widely used as the definition of hyperuricemia, considering the solubility of uric acid [3, 4]. However, uric acid levels in children and adolescents change during development.
Therefore, age- and sex-related reference values for uric acid should be considered for defining hyperuricemia in children and adolescents.
Summarizing previous reports, the following developmental changes in uric acid levels have been identified although the absolute uric acid values differ marginally from report to report [1, 5–7].
Uric acid levels increase gradually from birth to the end of elementary school age. Subsequently, levels rise sharply in males and slightly in females, creating a significant difference between the sexes. For reference, data from two studies [1, 6] are shown in Table 1.
|The number within brackets indicate the reference number. The blanks in this column indicate both sexes.|
Large-scale epidemiological studies of gout in children and adolescents are quite limited. In a study using data in the UK General Practice Research Database (1990–1999), Mikuls et al. report that the incidence of gout in individuals 7.0
4.5.4. Chronic Kidney Disease (CKD)
A recent review suggests that uric acid plays a role in the pathogenesis of CKD in children . Rodenbach et al. demonstrated that hyperuricemia was an independent risk factor for faster progression of CKD in a cohort of over 600 children and adolescents over a 5-year period . Furthermore, lowering of uric acid levels with allopurinol over a 4-month period improved eGFR independently in children with stage 1–3 CKD .
5. Treatment of Hyperuricemia
Apart from a causal relationship, it is clear that hyperuricemia and those four components of NCDs described above are closely associated each other. Hyperuricemia in children and adolescents is a target of treatment, considering the report demonstrating that pediatric patients with hyperuricemia are at increased risk of mortality, particularly due to kidney and cardiovascular diseases .
5.1. Lifestyle Intervention
Since obesity is a major cause of hyperuricemia in otherwise healthy children and adolescents, programs for reducing body weight by lifestyle intervention (dietary, physical activity, and behavioral changes) are important . To my best knowledge, however, only two studies addressing this issue are present in the literature. Togashi et al. demonstrated that uric acid levels decreased significantly in 33 obese children after diet plus exercise treatment for 3 months . Furthermore, a one-year weight reduction program in a cohort of 10–17-year-olds was reported to decrease uric levels in 86% of the females and 67% of the males . Although the effect of programs of intervening a lifestyle on obesity is promising, the effect on hyperuricemia requires further investigation over a longer observation period.
5.2. Xanthine Oxidase Inhibitors
Allopurinol, an inhibitor of xanthine oxidase, is an old drug commonly used to treat a variety of pediatric diseases [17, 25], including HGPRT deficiency , APRT deficiency , glycogen storage disease type Ia , and FJHN . In addition, the efficacy of allopurinol treatment alone  or in combination with enalapril  in reducing blood pressure has been investigated in children with hyperuricemic hypertension. However, allopurinol should be used with caution as it can cause severe skin side effects, including Stevens–Johnson syndrome (SJS). The association of allopurinol-induced SJS with human leukocyte antigen (HLA)-B ∗ 5801 has been identified .Febuxostat is a newly developed nonpurine, selective inhibitor of xanthine oxidase . Kaku and Nishimura administered febuxostat to 16 children with CKD and observed a renal protective effect accompanied by the lowering of uric acid levels . When used as prophylaxis for TLS in pediatric hematological malignancies, an effect comparable to that of allopurinol was observed . Further investigation is required to determine the efficacy and safety of febuxostat for use in children and adolescents.
5.3. Uric Acid Oxidase (Rasburicase)
A recombinant uric acid oxidase, rasburicase, is widely used for the prevention of hyperuricemia observed in TLS at diagnosis or during treatment of a variety of malignancies in children [91, 92]. Rasburicase treatment achieved a greater and more rapid decline in uric acid levels than did allopurinol . Despite the efficacy of rasburicase in malignancy-induced TLS, Cheuk et al. raised concerns about its serious side effects, including hypersensitivity and hemolysis .
6. Conclusion and Future Directions
This review raises three points that should be considered to improve and shape the direction of future research on hyperuricemia in children and adolescents. First, the reference values of uric acid in children and adolescents change with age, with a difference between the sexes arising at about 12 years of age. Therefore, the definition of hyperuricemia used in data analysis should take these factors into account. Second, future studies should address the question of how hyperuricemia arising in childhood or adolescence affects health in adulthood, especially regarding NCDs. Large cohort, long-term follow-up studies are needed to answer this question. Third, the treatment of hyperuricemia in children and adolescents should be investigated with the aim of standardization, including recommendations as to when uric acid-lowering treatment should be initiated and which drugs are most suitable. These factors are particularly important with respect to chronic diseases that cause hyperuricemia starting early in childhood. The efficacy of treatment through lifestyle intervention also should be investigated. As our understanding of the importance of hyperuricemia in childhood improves, pediatricians should pay greater attention to hyperuricemia in the clinical setting.
The work described has not been published before and is not under consideration by any other journals.
Conflicts of Interest
The author declares that there are no conflicts of interest.
The author would to thank Enago (www.enago.jp) for the English language reviews.Copyright © 2019 Masaru Kubota. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gout Caused by Genetics More Than Diet
One of the most common misconceptions about gout, according to an article by the Arthritis Foundation, is that diet is the primary cause.
Gout, or gouty arthritis, is a painful condition caused by a high level of uric acid in the blood that can lead to deposits of uric acid crystals in the joints and tissues.
Most often gout affects the big toe joint, but it can also occur in the hands, feet, wrists, ankles, knees, and elbows.
Uric acid is formed in the body naturally when compounds called purines are broken down.
Most uric acid (about two-thirds) is produced when our cells age and die, but about a third of uric acid in our bodies is produced by the breakdown of purines that are found in many foods and drinks.
Among the most purine-rich foods and drinks are red meat, shellfish, alcoholic beverages (especially beer), and sugary drinks. People with gout typically try to avoid foods and drinks these to try to lower the amount of uric acid in their bodies.
Various factors can contribute to elevated blood uric acid levels and the development of gout (e.g., joint damage, infection, medications, etc.
) The goals of a recent study published in The BMJ was to test various foods for links to uric levels and to determine within a general population the extent to which diet contributes to uric acid levels compared to inherited genetic variations.
Findings from the study suggest that, at least in a population without gout, genetics play a much larger role than diet in promoting high uric acid levels in the blood.
Importantly, the recognition of a significant genetic component to this condition may help reduce the stigmatization and embarrassment that some people have due to a condition that many see as self-inflicted and the result of unhealthy lifestyle habits. The hope is that this new information may help empower those people with gout who have been reluctant to seek help.
According to an accompanying editorial, the new research “provides important evidence that much of patients' preponderance to [high uric acid levels] and gout is [genetic and] non-modifiable, countering these harmful but well-established views and practices.”
The researchers collected and analyzed data from 8,414 men and 8,346 women of European ancestry from five ongoing population-based cardiovascular and nutrition studies in the United States.
Participants were excluded from this study if they had kidney disease or gout, or if they were taking uric acid-lowering drugs or diuretic drugs (water pills).
The participants filled out dietary surveys, had their blood uric acid levels measured, and underwent genetic testing.
By comparing the participants' survey answers with blood uric acid levels, the researchers found seven foods associated with raised uric acid levels (beer, liquor, wine, potato, poultry, soft drinks, and meat) and eight foods associated with lowered uric acid levels (eggs, peanuts, cold cereals, skim milk, cheese, brown bread, margarine, and non-citrus fruit). Even so, when they calculated how big an influence each of these foods had on uric acid levels, they found that individually, the food items explained less than 1% of variation in uric acid levels in all participants.
The researchers then used four diet scores to see if general diet patterns affected variations in uric acid levels. Overall, the diet scores explained less than 0.3% of the variation in urate levels in the study participants.
Next, the researchers looked at 30 gene variations previously linked to blood uric acid levels in Europeans (since the study participants were all of European descent). They discovered that these common inherited genetic variants in the participants' DNA could account for about 23.9% of the variation in uric acid levels.
For instance, variants in the SLC2A9 gene, a gene linked to the transport of uric acid in the kidneys, were the most strongly associated in varying uric acid levels, explaining about 4% of the variation in uric acid levels.
The researchers concluded that for their study participants, overall diet explained “much less variance in [uric acid] levels when compared with inherited genetic variants.”
The researchers acknowledged that the study had limitations. The data are specific to the European population without gout that they enrolled in their study. It is not clear whether their conclusions also apply to individuals with gout, since they were not studied.
This study was not designed to predict risk of developing gout or change treatment, and additional studies would be needed to determine whether individuals with these variants are more ly to develop gout. However, this work may impact people with gout and their healthcare providers by challenging “widely held community perceptions” that high uric acid levels are primarily caused by diet.
Common variants in the SLC28A2 gene are associated with serum uric acid level and hyperuricemia and gout in Han Chinese
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Genetics Drive Gout Risk Far More Than Diet
The assumption that gout is mainly caused by diet is wrong, according to a meta-analysis of diet and genetic variants in over 16,000 subjects. The analysis, which was published online today in BMJ, suggests that even the most “gout associated” foods and diets accounted for less than 1% of variance in serum urate levels, while nearly 24% of variance was explained by genetic factors.
“Our results challenge widely held community perceptions that hyperuricaemia is primarily caused by diet, showing that genetic variants have a much greater contribution to hyperuricaemia in the general population than dietary exposure,” write Tanya J. Major, PhD, and colleagues from University of Otago, New Zealand, and colleagues.
“People with gten experience stigma from the societal misconception that gout is a condition caused by dietary habits and an unhealthy lifestyle, a view which is also pervasive among healthcare professionals and in portrayals of gout in lay media,” write Lorraine Watson, PhD, and Edward Roddy, MD, from Keele University, UK, in an accompanying editorial.
“As a result, patients known to have gout are often reluctant to seek help for fear that they will not be taken seriously or will be blamed for their lifestyle habits….
The study by Major and colleagues provides important evidence that much of patients' predisposition to hyperuricaemia and gout is non-modifiable, countering these harmful but well established views and practices and providing an opportunity to address these serious barriers to reducing the burden of this common and easily treatable condition.”
Major and colleagues performed a meta-analysis of cross-sectional food frequency data from five US cohort studies. They systematically analyzed individual foods for associations with serum urate levels and compared the variances associated with dietary factors to those associated with common, genome-wide single-nucleotide variants.
The researchers also note that heritable differences include not only those directly associated with serum urate levels but also to differences in food preferences that might contribute to gout risk, such as consumption of coffee, alcohol, or sugar sweetened beverages.
The meta-analysis included 16,760 individuals of European ancestry (8414 men and 8346 women) from the US, all older than 18 years, without kidney disease or gout, and not taking urate lowering or diuretic drugs. The main outcome measures were average serum urate levels and variance in serum urate levels.
Mutivariable analyses included serum urate, dietary survey data, potential confounders (sex, age, body mass index, average daily calorie intake, years of education, exercise levels, smoking status, and menopausal status), and genome-wide genotypes.
To assess genetic risk, the team used 30 gene variants that have been previously associated with serum urate.
In the diet analysis, the researchers identified seven foods associated with raised serum urate levels, including beer, liquor, wine, potato, poultry, soft drinks, and meat (beef, pork, or lamb).
“The food items with the strongest urate raising effect (beer and liquor) were associated with a 1.38 μmol/L increase in serum urate per serving per week, equating to a 9.66 μmol/L (0.16 mg/dL) increase per daily serving.”
They also identified eight foods associated with reduced serum urate levels, including eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and non-citrus fruits.
Diet scores were constructed on the basis of four different healthy diet guidelines; three were associated with lower serum urate levels, and one was associated with raised serum urate levels, but none of these scores explained more than ≤0.3% of the variance in serum urate.
Individually, the 14 food items associated with serum urate variance explained 0.06% to 0.99% of the variation; summed, they explained 3.28% of the variation, and the diet scores explained less of the variation than the most strongly associated individual food item.
“In comparison, 23.9% of variance in serum urate levels was explained by common, genome wide single nucleotide variation,” the authors write. This included 23.8% in the male cohort and 40.3% in the female cohort.
Watson and Roddy comment, “Despite the authors' caution against extrapolating their findings [to non-European subjects or to those with evident gout], it is unly that the cause of hyperuricaemia in the studied populations is substantially different to those with clinically evident gout. The study does not provide evidence to support a change in guideline recommendations that patients with gout should modify their diet to avoid consuming certain high risk foods excessively; it does have other broad implications for people with gout and those who care for them.”
Specifically, Watson and Roddy explain that gout is often poorly managed, that two thirds of patients are not prescribed urate-lowering drugs, and that only a minority of patients increase the dose to the level required to achieve the low serum urate level needed to rid the body of urate crystals, prevent flares, and shrink tophi.
They conclude, “The reasons for poor management of gout are not fully understood, but patients' and practitioners' suboptimal understanding of gout, its causes, and treatment are considered to be important factors.”
The study was supported by the Health Research Council of New Zealand and the University of Otag.
Co author Nicola Dalbeth, MD, has received consulting fees, speaker fees, or grants from the following companies that have developed or marketed urate-lowering drugs for management of gout: Takeda, Ardea Biosciences/AstraZeneca, Cymabay/Kowa, and Crealta/Horizon. Tony R. Merriman, PHD, has received grants from Ardea Biosciences/AstraZeneca and Ironwood Pharmaceutical.
BMJ. Published online October 10, 2018. Full text, Editorial
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What Role Does Diet Play in Gout Management?
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Genetics of serum urate concentrations and gout in a high-risk population, patients with chronic kidney disease
- Chronic kidney disease
- Metabolic disorders
We evaluated genetics of hyperuricemia and gout, their interaction with kidney function and medication intake in chronic kidney disease (CKD) patients.
Genome-wide association studies (GWAS) of urate and gout were performed in 4941 CKD patients in the German Chronic Kidney Disease (GCKD) study. Effect estimates of 26 known urate-associated population-based single nucleotide polymorphisms (SNPs) were examined.
Interactions of urate-associated variants with urate-altering medications and clinical characteristics of gout were evaluated. Genome-wide significant associations with serum urate and gout were identified for known loci at SLC2A9 and ABCG2, but not for novel loci.
Effects of the 26 known SNPs were of similar magnitude in CKD patients compared to population-based individuals, except for SNPs at ABCG2 that showed greater effects in CKD. Gene-medication interactions were not significant when accounting for multiple testing. Associations with gout in specific joints were significant for SLC2A9 rs12498742 in wrists and midfoot joints.
Known genetic variants in SLC2A9 and ABCG2 were associated with urate and gout in a CKD cohort, with effect sizes for ABCG2 significantly greater in CKD compared to the general population. CKD patients are at high risk of gout due to reduced kidney function, diuretics intake and genetic predisposition, making treatment to target challenging.
Gout is a progressive painful debilitating disease, and the most common inflammatory arthritis in many Western countries1.
Population-based studies have identified genetic variants in multiple genes2 including SLC2A93,4,5 and ABCG25,6 associated with serum urate concentrations.
Individuals with chronic kidney disease (CKD) represent a high-risk population for hyperuricemia and gout due to decreased renal clearance of urate and consecutive increase in serum urate concentrations.
About ~25% of CKD patients from the prospective German Chronic Kidney Disease (GCKD) study reported a physician diagnosis of gout at study baseline and two thirds of patients were hyperuricemic7. This high prevalence of gout is most relevant given that CKD affects about 10% of the adult population in many countries8.
Despite the importance of CKD as a risk factor for gout, knowledge about genetic determinants of serum urate in the setting of CKD is limited.
One candidate gene study that focused on 11 urate transporters reported that the strength of association – as quantified by the association p-value – between genetic variants in ABCG2 was stronger in patients with CKD compared to 481 population-based individuals, while the opposite was observed for variants in SLC2A99. While the authors hypothesized that this could be interpreted by a compensatory role of the ABCG2 transporter in the intestine in the setting of reduced kidney function, they did not formally compare effect sizes or test for differences in effect. Additional aspects of urate genetics in CKD that have not been addressed are interactions between genetic risk variants for gout and medication intake as well as clinical characteristics of gout attacks.
We aimed to evaluate the genetic underpinnings of hyperuricemia and gout in a large cohort of CKD patients, by carrying out genome-wide association studies (GWAS) of serum urate concentrations and gout.
Effect sizes of known urate-associated variants detected in the general population were formally compared to their counterparts among CKD patients.
Interactions between medications influencing serum urate concentrations and commonly prescribed in CKD were evaluated, and associations between genetic risk variants and clinical characteristics of gout were examined.
Baseline clinical characteristics of 4,941 GCKD study participants with complete clinical information required for the GWAS are summarized in Table 1. A quarter of the patients reported diagnosis of gout at study baseline. Participants with gout compared to those without gout were significantly (p-value
Gout Risk Factor Less about Diet, More about Genes
Despite accumulating evidence that gout isn’t all about diet, the condition retains its reputation as the “rich man’s disease”—or the disease that afflicts those who eat richly, regardless of their fortunes. Back in 2008, a study appeared suggesting that about 12% of gout cases could be attributed to dietary causes.
A little later, additional studies identified genes that were associated with gout or gout’s chief risk factor, hyperuricemia, or elevated uric acid levels.
And now, a new study that has revisited the causes of hyperuricemia has concluded that in contrast with genetic contributions, diet explains very little of the variation in uric acid levels.
In the new study, scientists based in New Zealand found that diet scores explained less than 0.3% of variance in serum urate. In contrast, they determined that common, genome-wide single nucleotide variation explained 23.9% of the variance.
Additional details appeared recently in BMJ, in an article titled, “Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population-based cohorts.
” The article described how the scientists analyzed dietary survey data for 8,414 men and 8,346 women of European ancestry from five U.S. cohort studies.
Participants were aged over 18 without kidney disease or gout, and were not taking urate-lowering or diuretic drugs.
Blood urate measurements and genetic profiles were recorded. Factors that could have affected the results, such as sex, age, body mass index, daily calorie intake, education, exercise levels, and smoking status, were also considered.
Elevated serum urate levels were associated with seven foods: beer, liquor, wine, potato, poultry, soft drinks, and meat (beef, pork, or lamb). Reduced serum urate levels were associated with eight foods: eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and noncitrus fruits. Each of these foods, however, explained less than 1% of the variation in urate levels.
Similarly, three diet scores, healthy diet guidelines, were also associated with lowered urate levels, while a fourth, a diet high in unhealthy foods, was associated with increased urate levels.
Again, however, each of these diet scores explained very little (less than 0.3%) variance in urate levels.
In contrast, genetic analysis revealed that common genetic factors explained almost a quarter of the variation in urate levels.
“Our data are important in showing the relative contributions of overall diet and inherited genetic factors to the population variance of serum urate levels,” the authors of the BMJ research article indicated.
“Our results challenge widely held community perceptions that hyperuricaemia is primarily caused by diet, showing that genetic variants have a much greater contribution to hyperuricaemia in the general population than dietary exposure.”
In an accompanying editorial (“The role of diet in serum urate concentration“), researchers at Keel University pointed out that people with gten experience stigma from the misconception that it is a self-inflicted condition caused by unhealthy lifestyle habits and, as a result, are often reluctant to seek medical help.
This study, the Keel scientists wrote, “provides important evidence that much of patients' preponderance to hyperuricaemia and gout is nonmodifiable, countering these harmful but well-established views and practices and providing an opportunity to address these serious barriers to reducing the burden of this common and easily treatable condition.”