A causal relationship between high density lipoprotein cholesterol (HDL-C) and gout was established in a Mendelian randomization study published in the Journal of Human Genetics.<\/p>\n
Genetic data and HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations from 110,347 individuals of European ancestry included in the Global Lipids Genetics Consortium were examined in relation to a gout diagnosis (n=69,374) using additive regression adjusted for covariates.<\/p>\n
A significant relationship between HDL-C and gout was observed: for every 12.26 mg\/dL increase in HDL-C, the odds of having gout were decreased (odds ratio [OR], 0.75; 95% CI, 0.62-0.91; P =3.3110-3).<\/p>\n
To further examine the relationship between HDL-C and gout, the investigators employed a leave-one-out approach to test the contribution of 92 instrumental HDL-C variables. The 2 largest effects were observed for the gene Aldehyde Dehydrogenase 1 Family Member A2 (ALDH1A2) and microRNA AC012181.1. The effect sizes of these 2 variables were low and did not affect the association between HDL-C and gout (OR, 0.74; 95% CI, 0.60-0.91; P =4.1810-3).<\/p>\n
Concentrations of other lipids did not significantly alter odds of having gout. For every 30.25 mg\/dL increase in LDL-C, the OR for gout was 0.81 (95% CI, 0.61-1.07; P =.079). A 36.32 mg\/dL increase in TC was associated with an OR for gout of 0.98 (95% CI, 0.90-1.06; P =.604) and a 112.33 mg\/dL increase in TG was associated with an OR of 1.16 for gout (95% CI, 0.93-1.45; P =.186).<\/p>\n
Serum urate was negatively associated with HDL-C (estimated causal effect, -0.09; 95% CI, -0.12 to -0.05; P =7.0010-4) and positively associated with TG (estimated causal effect, 0.10; 95% CI, 0.06-0.14; P =9.8710-5).<\/p>\n
Using a mediation analysis, the total effect of HDL-C on gout was -0.154 (95% CI, -0.256 to -0.051; P =3.3110-3), the direct effect was -0.106 (95% CI, -0.189 to -0.022; P =1.3510-2), and the mediation effect was -0.020 (95% CI, -0.033 to -0.008; P =1.6710-3). The mediation effect accounted for 13.0% of the total variance, indicating that urate may be an important mediator of gout and HDL-C.<\/p>\n
In the mediation analysis, TG had a similar but inverse relationship, in which the total effect on gout was 0.082 (95% CI, -0.039 to 0.202; P =1.8610-1), the direct effect was 0.048 (95% CI, -0.057 to 0.152; P =3.71101), and the mediation effect was 0.023 (95% CI, 0.0100.037; P =8.39104). This mediation effect of urate on gout accounted for 28.0% of the total variance.<\/p>\n
This study was limited by its sample size. Although the study included tens of thousands of adults with gout, the cases only represented 3.1% of the total dataset, possibly limiting the study power.<\/p>\n
These data confirmed the causal association between HDL-C and TG with gout and found that serum urate levels likely mediate these relationships.<\/p>\n
Reference<\/p>\n
Yu X, Wang T, Huang S, et al. Evaluation of the causal effects of blood lipid levels on gout with summary level GWAS data: two-sample Mendelian randomization and mediation analysis. [published online October 25, 2020] J Hum Genet. doi:10.1038\/s10038-020-00863-0<\/p>\n
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See original here: A causal relationship between high density lipoprotein cholesterol (HDL-C) and gout was established in a Mendelian randomization study published in the Journal of Human Genetics. Genetic data and HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations from 110,347 individuals of European ancestry included in the Global Lipids Genetics Consortium were examined in relation to a gout diagnosis (n=69,374) using additive regression adjusted for covariates. A significant relationship between HDL-C and gout was observed: for every 12.26 mg\/dL increase in HDL-C, the odds of having gout were decreased (odds ratio [OR], 0.75; 95% CI, 0.62-0.91; P =3.3110-3) Continue reading
\nCausal Association Between HDL-C, TG and Gout Identified - The Cardiology Advisor<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"