| Hyperuricemia(HU)is a chronic metabolic disease caused by metabolic disorders of purine.It is mainly caused by excessive uric acid secretion or renal excretion disorders,and characterized by higher serum uric acid level than normal.The prevalence of HU in different ethnic groups was 2.6%-36%,which showed a significant increase and younger trend in recent years.In 2015,the overall prevalence of HU in mainland China was 13.3%.HU has become another common metabolic disease after diabetes.Hu is the most direct cause of gout,and many studies have shown that Hu is closely related to the occurrence and development of metabolic syndrome,cardiovascular diseases,chronic kidney disease and other diseases.In addition,Hu is an independent predictor of premature death.HU is the combined effects of genetic and environmental factors.Environmental factors,especially the dietary intake,play a very important role in occurrence and development of HU.As one of the three major energy-supplying nutrients,lipids are indispensable.Studies have shown that lipid metabolism is associated with HU.On the one hand,elevated serum lipid level(such as triglyceride and total cholesterol)were found to positively correlated with serum uric acid level and the prevalence of HU.On the other hand,high level of serum uric acid is a risk factor for lipid metabolic disorders such as hyperlipoproteinemia and lipid storage disorder,and studies have suggested that serum uric acid is an independent predictor of non-alcoholic fatty liver disease in Chinese adults.As the most important component of lipids,fatty acids have many types and different functions.Many studies have shown that different types and composition of fatty acids have different effects on metabolic diseases such as diabetes and hypertension.For example,palmitic acid and stearic acid are risk factors of type 2 diabetes,while C15:0 and c17:0 are protective factors,although they are all saturated fatty acids.In addition,due to the structural similarity and mutual transformation among fatty acids,the interaction between fatty acids is likely to be ignored.Therefore,in recent years,more studies have focused on the association between fatty acid patterns and metabolic diseases,and found that fatty acid patterns can provide more guidance for the prevention of metabolic diseases.The main source of serum fatty acids is the mutual conversion of fatty acids and dietary intake.The randomized controlled trials have suggested that dietary supplementation with n-3 polyunsaturated fat can significantly reduce the risk of gout attack in adult men.Although HU is the most direct cause of gout and the basis of many metabolic diseases,few studies have evaluated the association between various fatty acids and HU.Therefore,the aim of this study is to investigate the association between circulating fatty acid subtypes,fatty acid pattern,as well as dietary fatty acid with odds of HU.The main contents of this study are as follows:Part One: Association of circulating fatty acids and hyperuricemiaObjective: To explore the association of plasma fatty acid subtypes,individual fatty acid with odds of HU.Methods: We used the data from the National Health and Nutrition Examination Survey(NHANES)2003–2004 and NHANES 2011-2012 in this part.Participants over the age of 20 with complete blood fatty acid and uric acid data were enrolled,while those with abnormal energy intake(< 500 kcal/d or > 5000 kcal/d)and pregnant women were excluded.The general characteristics of the population were analyzed by t test,Wilcoxon rank sum test and chi–square test.We apply multivariate Logistic regression to investigate the association between circulating fatty acid subtypes,individual fatty acid and the odds of HU in the whole population and the subgroups with normal and high TG level.Adjustments were made for potential counding factors,including gender,age,race,Body mass index(BMI),education status,smoking status,alcohol consumption status,hypertension,diabetes,cardiovascular disease status,TG,HDL-C,glomerular filtration rate,energy.The results were expressed as Odd Ratio(OR)with 95% Confidence interval(95% CI).Result: This part of study included a total of 2740 participants,including 513 patients with HU and 2227 patients without HU.Participants with HU displayed significantly higher concentrations of total fatty acid than those without HU(median: 12.42(10.33-14.72)mmol/L and 11.28(9.61-13.13)mmol/L,respectively,P < 0.01).In the multivariate Logistic regression of the association of fatty acid subtypes and HU,after adjustment,the OR with 95% CI of HU was 0.41(0.24,0.72)for the highest versus the lowest quartile of n-6 PUFAs.The OR with 95% CI of HU was 1.62(1.01,2.67)for the highest versus the lowest quartile of SFAs.In the multivariate Logistic regression of the association of individual fatty acid and HU,after adjustment,the ORs with 95% CIs of HU were 1.84(1.21,2.81)and 2.56(1.52,4.32)for the highest versus the lowest quartile of C16:0 and C16:1 n-7,respectively.The ORs with 95% CI of HU were 0.61(0.41,0.93)and 0.57(0.37,0.86)for the highest versus the lowest quartile of C20:0 and C18:2 n-6,respectively.Similar results were aklso found in participants with normal TG level.And there was no association between the levels of fatty acids and Hu in the participant with high TG level.Conclusions: This part of the study indicated that higher concentrations of SFAs,C16:0,C16:1 n-7 and lower concentrations of C20:0,C18:2 n-6 were significantly associated with higher odds of HU.The association between fatty acid level and HU in participants with normal TG level was similar to the above.Part Two: Association of fatty acid pattterns and odds of hyperuricemia:bsaed on factor analysisObjective: To investigate the association of the combined effect of multiple fatty acids(fatty acid pattern)and the odds of HU.Methods: The data source and the inclusion criteria of the participants were the same as the part one.Factor analysis was used to derive fatty acid patterns from all participants and subgroups with normal and high TG level.The scores of each fatty acid pattern of the participants were calculated using the factor scoring coefficient.The association of the score of fatty acid pattern and the odds of HU was investigated through multivariate Logistic regression.Results: Five fatty acid patterns were derived from the whole participants and the subgroup with high TG,and the scores of each fatty acid pattern were not significantly associated with the odds of HU.Six fatty acid patterns were identified from thesubgroup with normal TG and explained17.37%,15.65%,13.97%,13.11%,11.97 and 8.16% of the overall variability,respectively.After adjustment,the ORs with 95% CIs of HU were 1.72(1.05,2.84)and 1.77(1.05,3.12)for the highest versus the lowest quartile of FAP1 and FAP3,respectively.The first pattern was partly characterized by higher concentrations of C14:0,C16:0,C14:1 n-5 and C16:1 n-7.The third pattern was partly characterized by higher concentrations of C18:1 n-9,C18:1 n-7,C20:1 n-9 and C20:2 n-6.Conclusions: The combined effect of multiple monounsaturated fatty acids and multiple saturated fatty acids may be a risk factor for the odds of HU in the participants with normal TG level.Part Three: Association of dietary polyunsaturated fatty acids and hyperuricemiaObjective: To investigate the association of dietary polyunsaturated fatty acids intake and the odds of HU.Methods: We used the data from the NHANES 2003-2016 in this part.Participants older than 20 years with complete dietary fatty acid and blood uric acid data were enrolled,while those with abnormal energy intake(< 500 kcal/d or > 5000 kcal/d)and pregnant women were excluded.The general characteristics of the population were analyzed with the same method as the part one.The multivariate Logistic regression was used to investigate the association between n-3 PUFAs,n-6 PUFAs,n-3/n-6 PUFAs,ALA,LA and the odds of HU.Sensitivity analysis was conducted to explore the stability of the results by changing the diagnostic criteria of HU,excluding participants with gout and participants with chronic kidney disease.The effects of substitution of n-3 PUFAs and n-6 PUFAs with other fatty acids on the odds of HU were investigated by using the isocaloric substitution model.Results: This part of study included a total of 26323 participants,including 4916 patients with HU and 21407 patients without HU.After adjustment,the ORs with 95% CI of HU were 0.81(0.66,0.99),0.81(0.67,0.98),0.73(0.58,0.92)and 0.81(0.67,0.98)for the highest versus the lowest quartile of n-3 PUFAs,n-6 PUFAs,ALA and LA,respectively.The results of the isocaloric substitution model showed that the substitution of n-3PUFAs and n-6 PUFAs for other fatty acids had no significant effect on the odds of HU.And the results of sensitivity analysis were basically consistent with the results of multivariate Logistic regression.Conclusion: Dietary intake of n-3 PUFAs,n-6 PUFAs,ALA and LA can significantly reduce the risk of HU. |
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