903 Cardona, et al: Urate-lowering diet Response to a Urate-Lowering Diet According to Polymorphisms in the Apolipoprotein AI-CIII-AIV Cluster FERNANDO CARDONA, FRANCISCO J. TINAHONES, EDUARDO COLLANTES, EDUARDO GARCIA-FUENTES, ALEJANDRO ESCUDERO, and FEDERICO SORIGUER ABSTRACT. Objective. The apolipoprotein AI-CIII-AIV cluster has been associated with the response to a urate- lowering diet, and polymorphisms in the apolipoprotein CIII gene have been associated with hype- ruricemia and hypertriglyceridemia. We assessed the influence of polymorphisms in the apolipopro- tein AI-CIII-AIV cluster on the response to a urate-lowering diet in patients with hyperuricemia. Methods. A urate-lowering diet was followed for 2 weeks by 64 men with hyperuricemia. Plasma concentrations of triglycerides, cholesterol, glucose, and uric acid, and the uric acid clearance and 24-hour uric acid urinary excretory fraction were measured before and after the diet. The data were analyzed in association with the polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster. Results. After the urate-lowering diet, the plasma levels of triglycerides, cholesterol, glucose, and uric acid and 24-hour uric acid excretion all fell significantly. Paired sample ANOVA showed that the decrease was mainly due to the diet, except for the plasma triglycerides, which were influenced by allele X2 of the XmnI polymorphism of the apolipoprotein AI gene. Conclusion. The response of the biological variables to a urate-lowering diet was mainly influenced by diet. Changes in triglycerides were also influenced by the apolipoprotein AI XmnI polymorphism (p = 0.04), suggesting a gene-diet interaction (p = 0.03). (J Rheumatol 2005;32:903–5) Key Indexing Terms: HYPERURICEMIA APOLIPOPROTEIN AI-CIII-AIV GENE CLUSTER DIET From the Rheumatology Service, Hospital Reina Sofia, Cordoba; and the Endocrinology and Nutrition Service, Hospital Civil, Carlos Haya University Hospital, Málaga, Spain. Supported by grants from the Instituto de Salud Carlos III. F. Cardona, PhD; F.J. Tinahones, MD, PhD; E. Garcia-Fuentes, PhD; F. Soriguer, MD, PhD, Endocrinology and Nutrition Service, Hospital Civil, Carlos Haya University Hospital; E. Collantes, MD, PhD; A. Escudero, MD, Rheumatology Service, Hospital Reina Sofia. The investi- gation group belongs to the Red de Centros de Metabolismo y Nutrición (RCMN, C03/08) of the Instituto de Salud Carlos III, Madrid, Spain. Address reprint requests to Dr. F.J. Tinahones, Servicio de Endocrinología y Nutrición pabellon 1 sotano, Hospital Civil, Plaza del Hospital Civil s/n 29009, Malaga, Spain. E-mail: fjtinahones@terra.es Submitted April 19, 2004; revision accepted October 14, 2004. Hyperuricemia, which is associated with obesity, dyslipi- demia, and the insulin resistance syndrome, is influenced by dietary factors. The varied response to dietary intervention may have a strong genetic component 1 . The association between polymorphisms of the apolipoprotein AI-CIII-AIV cluster and plasma lipids, cardiovascular disease, and interindividual variations in the response to dietary therapy have all been studied 2 . Apolipoprotein AI polymorphism is involved in the vari- ability of the apolipoprotein AI response to changes in dietary fat. In one polymorphism, a G to A transition 75 bp upstream has recently been shown to have a significant effect on the response to changes in the amount of dietary fat 3 . The frequency of the apolipoprotein CIII mutated allele S2 varies greatly between different racial groups. This allele is associated with decreased plasma concentrations of cho- lesterol, low density lipoprotein (LDL) cholesterol, and apolipoprotein B after a monounsaturated fatty acid-rich diet 4 . However, few studies have assessed the role of poly- morphisms of the whole cluster in hyperuricemia. We eval- uated the influence of polymorphisms in the whole apolipoprotein AI-CIII-AIV cluster in the response to a urate-lowering diet in patients with hyperuricemia. MATERIALS AND METHODS Subjects. The study was undertaken in 64 men with gout, based on the American College of Rheumatology criteria of Wallace, et al 5 . No patient was receiving lipid-lowering or urate-lowering therapy and patients with secondary hyperuricemia (renal failure or use of diuretics), diabetes after an oral glucose tolerance test, and hypothyroidism were excluded, as were patients with alcohol abuse. Biochemical variables were measured before and after a urate-lowering diet 6 , which was achieved through dietary advice. The diet includes most sugars, starches, and fats. Protein is supplied chiefly by eggs and cheese, and partly by bread, fruit, and nuts. The usual fluid intake is maintained and no restriction is placed on the amount of food consumed. The following foods are forbidden: meat, poultry, other flesh, fish, seafood, sardines, herrings, kidney, liver, meat extract, alcohol, beans, peas, lentils, spinach, oatmeal, and asparagus. Procedures. DNA was isolated 7 and amplified by polymerase chain reac- tion. Primers for the XmnI locus were those described by Shoulders, et al 8 ; by Jeenah, et al 9 for the –75 bp locus of the apolipoprotein AI gene (deter- mined by MspI); and by Dammerman, et al 10 for the SstI locus of the apolipoprotein CIII gene. Statistical analysis. Data are expressed as the mean ± standard deviation (SD). Comparison between groups was by Student t test for independent Personal non-commercial use only. The Journal of Rheumatology Copyright © 2005. All rights reserved. www.jrheum.org Downloaded on August 7, 2022 from